Conjugation of antibiotic resistance in Streptococcus suis.
Forty-eight clinical isolates of Streptococcus suis were examined for antibiotic sensitivity and the presence of plasmid DNA. It was determined that isolates from this study showed a substantial increase in resistance to erythromycin (ery), clindamycin, and tetracycline (tet) compared to a similar study conducted five years earlier. Eleven of the 48 isolates contained plasmid DNA as revealed by DNA isolation and gel electrophoresis. Plasmid DNA from four strains resistant to the above three antibiotics was tested for the ability to transform an antibiotic sensitive recipient. No transformation of antibiotic resistance could be demonstrated. In other experiments, the above four strains, along with four plasmid-negative triply resistant strains were tested for the ability to transfer tet or ery resistance to tet and ery sensitive recipients by conjugation. In each mating, antibiotic resistance was transferred at frequencies averaging 2.4 x 10(-6) recombinants/recipient for ery and 3.4 x 10(-6) recombinants/recipient for tet resistance. DNA from each clinical specimen, as well as the recombinants mentioned above was probed with tn916. Autoradiographs revealed that several clinical isolates and recombinants bound the probe. It is concluded that conjugation of antibiotic resistance in these clinical strains is possibly mediated by a transposon similar to tn916.


Matched Child Savings Accounts in Low-Resource Communities: Who Saves?
This study examines variations in saving behavior among poor families enrolled in a Child Savings Account program for orphaned and vulnerable school-going children in Uganda. We employ multilevel analyses using longitudinal data from a cluster-randomized experimental design. Our analyses reveal the following significant results: (1) given the average number of months during which the account was open (18 months), families saved on average, USD 54.72, which, after being matched by the program (2:1 match rate) comes to USD 164.16-enough to cover approximately five academic terms of post-primary education; (2) children's saving behavior was not associated with quality of family relations; it was, however, significantly associated with family financial socialization; (3) family demographics were significantly associated with children's saving behavior in the matched Child Savings Account program; and (4) children enrolled in some schools saved better compared to children enrolled in other schools within the same treatment group.


Antiestrogens as chemopreventive agents in breast cancer: promise and issues in evaluation.
Tamoxifen citrate, the most extensively evaluated antiestrogen, acts primarily as a cytostatic agent by binding to the estrogen receptor. In rodent mammary model systems, when tamoxifen is given continuously after exposure to a carcinogen, the majority of expected tumors do not develop. In humans, adjuvant tamoxifen therapy, particularly when given for several years, is associated with significant improvement in relapse-free, and, in some studies, absolute survival. These benefits are achieved without major clinical toxicity and have led to suggestions that the use of tamoxifen as a chemopreventive agent in breast cancer be evaluated. In considering timing, optimal study population, study design, and methods for a chemoprevention trial using tamoxifen, the need for further data on the pharmacologic, biologic, and symptomatic effects of this agent becomes clear. Studies addressing this need are in progress and combined with ancillary data developed from ongoing adjuvant studies, should provide the critical information within the next few years.


Femoral loads during passive, active, and active-resistive stance after spinal cord injury: a mathematical model.
The purpose of this study was to estimate the loading environment for the distal femur during a novel standing exercise paradigm for people with spinal cord injury. A mathematical model based on experimentally derived parameters. Musculoskeletal deterioration is common after spinal cord injury, often resulting in osteoporotic bone and increased risk of lower extremity fracture. Potential mechanical treatments have yet to be shown to be efficacious; however, no previous attempts have been made to quantify the lower extremity loading during passive, active, and active-resistive stance. A static, 2-D model was developed to estimate the external forces; the activated quadriceps forces; and the overall bone compression and shear forces in the distal femur during passive (total support of frame), active (quadriceps activated minimally), and active-resistive (quadriceps activated against a resistance) stance. Passive, active, and active-resistive stance resulted in maximal distal femur compression estimates of approximately 45%, approximately 75%, and approximately 240% of body weight, respectively. Quadriceps force estimates peaked at 190% of body weight with active-resistive stance. The distal femur shear force estimates never exceeded 24% of body weight with any form of stance. These results support our hypothesis that active-resistive stance induces the highest lower extremity loads of the three stance paradigms, while keeping shear to a minimum. This model allows clinicians to better understand the lower extremity forces resulting from passive, active, and active-resistive stance in individuals with spinal cord injury.


How audience and general music performance anxiety affect classical music students' flow experience: A close look at its dimensions.
Flow describes a state of intense experiential involvement in an activity that is defined in terms of nine dimensions. Despite increased interest in understanding the flow experience of musicians in recent years, knowledge of how characteristics of the musician and of the music performance context affect the flow experience at the dimension level is lacking. In this study, we aimed to investigate how musicians' general music performance anxiety (MPA) level (i.e., the general tendency to experience anxiety during solo music performances) and the presence of an audience influence the nine flow dimensions. The participants were 121 university music students who performed solo a music piece once by themselves (private performance) and once in front of an audience (public performance). Their general MPA level was measured with an adapted version of the STAI and ranged from 27 (very low MPA) to 76 (very high MPA). The level of the nine flow dimensions was assessed with the Flow State Scale-2 after each performance. The levels of "concentration on task at hand," "sense of control," and "autotelic experience" decreased significantly with increasing general MPA level. The levels of "unambiguous feedback" and "loss of self-consciousness" decreased significantly with increasing general MPA level during the public performance only. The level of "sense of control" was significantly lower during the public performance than the private performance across participants. The level of "unambiguous feedback" was significantly lower during the public performance than the private performance for participants with a general MPA level higher than 47. The level of "loss of self-consciousness" was significantly lower during the public performance than the private performance for participants with a general MPA level higher than 32. In contrast, the general MPA level and the audience did not significantly affect the levels of "challenge-skill balance," "clear goals," and "action-awareness merging." These results show that the effects of general MPA level and audience vary greatly across flow state dimensions. We conclude that musicians' flow state should be analyzed at the dimension level rather than as a global score. We discuss how our findings could inform the development and implementation of interventions.


Impact of antiviral therapy on risk prediction model for hepatocellular carcinoma development in patients with chronic hepatitis B.
Risk prediction models for hepatocellular carcinoma (HCC) development are available. However, the influence of antiviral therapy (AVT) on these models in patients with chronic hepatitis B is unknown. The dynamic changes in risk prediction models during AVT and the association between risk prediction model and the risk of chronic hepatitis B-related HCC development were investigated. Between 2005 and 2017, 4917 patients with chronic hepatitis B (3361 noncirrhotic, 1556 cirrhotic) were recruited. The mean age of the study population was 49.3 years and 60.6% (n = 2980) of the patients were male. The mean Chinese University-HCC (CU-HCC) score was 12.7 at baseline in the overall study population, and decreased significantly (mean, 8.7) after 1 year of AVT (p < 0.001). The score was maintained throughout 5 years of AVT (mean, 8.4-8.8; p > 0.05). The proportion of high-risk patients (CU-HCC score ≥ 20) was 28.9% at baseline, and decreased significantly after 1 year of AVT (5.0%; p < 0.001), and remained stable through 5 years of AVT (2.2%-3.6%; p > 0.05). In addition to the score at baseline, the CU-HCC score at 1 year of AVT independently predicted the risk of HCC development (hazard ratio = 1.072; p < 0.001), together with male gender and platelet count (all p < 0.05). The CU-HCC score significantly decreased at 1 year of AVT and was maintained thereafter. The CU-HCC score after 1 year of AVT independently predicted the risk of HCC development in patients with chronic hepatitis B.


The role of semiochemicals in short-range location of aggregation sites in Adalia bipunctata (Coleoptera, Coccinellidae).
To survive unfavorable periods, ladybird beetles form conspicuous aggregations in specific microsites, with these locations remaining the same year after year. This constancy of location leads to the hypothesis that semiochemicals are involved in the attraction and aggregation of ladybirds to the microsite. In this study, we identified two types of semiochemicals that could play key roles in the attraction and aggregation formation of the two-spotted ladybird, Adalia bipunctata. We first isolated and identified three alkylmethoxypyrazines from A. bipunctata and tested the behavioral responses of diapausing ladybirds to these chemicals in a four-way olfactometer. This revealed that 2-isobutyl-3-methoxypyrazine, on its own or as part of a two-component mixture with 2-isopropyl-3-methoxypyrazine, elicited a positive behavioral response, causing arrestment of diapausing A. bipunctata. As ladybirds are in contact with each other in aggregations, we investigated the role of cuticular hydrocarbons (CHCs) in driving the cohesion and maintenance of aggregation. When an extract of CHCs from diapausing ladybirds was deposited near an alkylmethoxypyrazine source, ladybirds spent more time in the vicinity of the source. We identified a set of CHCs specific to diapausing A. bipunctata. Alkylmethoxyyrazines and CHCs thus deliver information to diapausing ladybirds searching for an aggregation site, as well as mediating several other behaviors throughout the ladybird's life cycle. Chemical parsimony is discussed.


Thermal stability of benzorods: molecular-dynamics simulations.
Thermal stability of benzorods 2C6-20C6, which are obtained by stacking n (n=2-20) dehydrogenated benzene, have been investigated by molecular-dynamics simulations. It has been found that these structures assume a geometrical form depending on the number of dehydrogenated benzene layers, and they are stable under heat treatment up to elevated temperatures with a dependence on length.


Mechanism of allosteric regulation of the rod cGMP phosphodiesterase activity by the helical domain of transducin alpha subunit.
The G protein alpha subunit (Galpha) is composed of two distinct folding domains: a GTP-binding Ras-like domain and an alpha helical domain (HD). We have recently reported that the helical domain (HDt) of the vertebrate visual transducin alpha subunit (Galphat) synergizes activation of retinal cyclic GMP phosphodiesterase (PDE) by activated Galphat (Liu, W., and Northup, J. K., (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 12878-12883). Here, we examine the molecular basis for this HD-based signaling regulation, and we provide a new model for the activation of the target effector. The HD proteins derived from visual transducin or taste gustducin alpha subunits, but no other Galpha HD proteins, each attenuate the PDE catalytic core (Palphabeta) and synergize Galphat stimulation of the holoPDE (Palphabetagamma2) with similar apparent affinities. The data from studies of both HDt-mediated attenuation and stimulation indicate that the HDt and the PDE inhibitory subunit (Pgamma) interact with PDE at independent sites and that Palphabeta contains the binding sites for HD. The saturation of both processes by HDt displays positive cooperativity with Hill coefficients of 1.5 for the attenuation of Palphabeta activity and 2.1 for synergism of holoPDE activation. Our data suggest the that Galphat-HDt regulates PDE by allosterically decreasing the affinity of Palphabeta for Pgamma and thus simultaneously facilitating the interaction of the activated Galphat-Ras-like domain with Pgamma. Thus, we propose a new model for the high efficiency of PDE activation as well as deactivation, and, overall, a novel mechanism for controlling fidelity, sensitivity, and efficacy of G protein signaling.


Lithium Sulfur Primary Battery with Super High Energy Density: Based on the Cauliflower-like Structured C/S Cathode.
The lithium-sulfur primary batteries, as seldom reported in the previous literatures, were developed in this work. In order to maximize its practical energy density, a novel cauliflower-like hierarchical porous C/S cathode was designed, for facilitating the lithium-ions transport and sulfur accommodation. This kind of cathode could release about 1300 mAh g(-1) (S) capacity at sulfur loading of 6 ~ 14 mg cm(-2), and showed excellent shelf stability during a month test at room temperature. As a result, the assembled Li-S soft package battery achieved an energy density of 504 Wh kg(-1) (654 Wh L(-1)), which was the highest value ever reported to the best of our knowledge. This work might arouse the interests on developing primary Li-S batteries, with great potential for practical application.


The specific targeting of immune regulation: T-cell responses against Indoleamine 2,3-dioxygenase.
Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme that is implicated in suppressing T-cell immunity in many settings including cancer. In recent years, we have described spontaneous CD8(+) as well as CD4(+) T-cell reactivity against IDO in the tumor microenvironment of different cancer patients as well as in the peripheral blood of both cancer patients and to a lesser extent in healthy donors. We have demonstrated that IDO-reactive CD8(+) T cells were peptide-specific, cytotoxic effector cells, which are able to recognize and kill IDO-expressing cells including tumor cells as well as dendritic cells. Consequently, IDO may serve as a widely applicable target for immunotherapeutic strategies with a completely different function as well as expression pattern compared to previously described antigens. IDO constitutes a significant counter-regulatory mechanism induced by pro-inflammatory signals, and IDO-based immunotherapy may consequently be synergistic with additional immunotherapy. In this regard, we have shown that the presence of IDO-specific T cells boosted immunity against CMV and tumor antigens by eliminating IDO(+) suppressive cells and changing the regulatory microenvironment. The current review summarizes current knowledge of IDO as a T-cell antigen, reports the initial results that are suggesting a general function of IDO-specific T cells in immunoregulation, and discusses future opportunities.


The use of anaphoric pronouns by French children in narrative: evidence from constrained text production.
This paper describes the acquisition of the 3rd person pronoun 'il/elle' (he, she, it) in seven to twelve-year-old French children (N = 58), in written production. An experiment was conducted to examine the relationship between the use of this anaphoric pronoun and the accessibility of the memory-trace of the corresponding referent in the texts. Referential accessibility in short texts was varied according to three factors: referential distance, thematization of the agent role (first sentence subject), and discourse focus. We found that the children were sensitive to the distance factor as early as 7;0, i.e. they used fewer personal pronouns when the referential distance increased. However, children of different ages differed in their weighting of the discourse focus factor and the thematization factor: the seven-year-olds (N = 18) and the eleven-year-olds (N = 20) were sensitive to variation of the discourse focus but not the thematization factor, while for the nine-year-olds (N = 20) it was the reverse. The main results suggest: (a) when seven and nine-year-olds use the pronoun 'il/elle', they do not comply with the constraints associated with the accessibility of the memory-trace of the referent; (b) memory constraints have an effect from the age of 7;0, but only when the discourse focus is maintained. It was concluded that the discourse management of the French personal pronoun 'il/elle' is not totally mastered at 11;0: children cannot operationally integrate the whole array of constraints implied in anaphoric management.


Are single entry communities and cul-de-sacs a barrier to active transport to school in 11 elementary schools in Las Vegas, NV metropolitan area?
Single entry communities (SECs) and cul-de-sacs minimize route choices and increase trip distance. Las Vegas' built environment facilitates the examination of these variables and active transport to school (ATS) rates. The purpose of this study was to examine the influence of SECs and cul-de-sacs on ATS rates in Las Vegas, NV elementary children. Parental-reported data was collected from 11 elementary schools on ATS rates (n = 1217). SECs and cul-de-sacs were quantified for each school zone. Logistic regression models were used to predict ATS. 23.9% of students reported ATS all of the time and 31.4% some of the time. SECs per school zone ranged from 0 to 25 (mean = 11.9). Cul-de-sacs ranged from 12 to 315 (mean = 138.3). Some ATS use was predicted by distance from school (p ≤ 0.001;OR = 0.61), parental education (high school: p = 0.004;OR = 0.53, some college: p = 0.001;OR = 0.50, 4 year degree: p = 0.004;OR = 0.52) and cul-de-sacs (p ≤ 0.001;OR = 0.99). A separate model using distance from school (p ≤ 0.001;OR = 0.61), parental education (high school: p = 0.002;OR = 0.51, some college: p ≤ 0.001;OR = 0.45, 4 year degree: p ≤ 0.001;OR = 0.45) and SECs (p ≤ 0.001;OR = 0.96) predicted some ATS. All ATS use was predicted by distance from school (p ≤ 0.001;OR = 0.58), parental education (Grades 9-11: p = 0.05;OR = 0.61, high school: p ≤ 0.001;OR = 0.45, some college: p ≤ 0.001;OR = 0.41, 4 year degree: p ≤ 0.001;OR = 0.38) and SECs (p ≤ 0.001;OR = 0.97). A separate model using distance from school (p ≤ 0.001;OR = 0.58), parental education (Grades 9-11: p = 0.041;OR = 0.59, high school: p ≤ 0.001;OR = 0.47, some college: p ≤ 0.001;OR = 0.44, 4 year degree: p ≤ 0.001;OR = 0.43) and cul-de-sacs (p ≤ 0.001;OR = 0.99) predicted all ATS. Current findings reveal that both SECs and cul-de-sacs were predictors of ATS beyond distance. Students with more SECs and cul-de-sacs in their school zone were less likely to utilize ATS.


Seroprevalence of human immunodeficiency virus, hepatitis B and C viruses among haemodialysis patients in two newly opened centres in Cameroon.
Haemodialysis (HD) patients are potentially susceptible to infection with blood borne viral agents especially; Human Immunodeficiency Virus (HIV), hepatitis B (HBV) and hepatitis C Viruses (HCV), compared to the general population. We described their epidemiology in two newly created haemodialysis units in Cameroon: the Buea and Bamenda haemodialysis centres. A cross sectional study: included were patients who had spent at least three months in haemodialysis. HBV, HCV and HIV serologies were determined and patients' characteristics extracted from patient's records. We included 104 participants (44 in Buea and 60 in Bamenda). Mean age was 48 years and 65.4% were men. Median duration in dialysis was 14 months. One of the three viral markers was present in 40.1% of patients. The hepatitis B surface antigen, anti-HCV and anti-HIV antibody prevalence were respectively 10.6%, 19.2%, 13.5%. A history of sexually transmitted infection was the only variable associated with anti-HIV antibody positivity. The sero-prevalence of HBsAg, HCV and HIV are high in the two centres. HIV prevalence may have reflected its etiology as a cause of ESKD. HCV remains a cause for concern and needs further evaluation. There is urgent need for the implementation of preventive and control measures.


Perceptions of a good death: A qualitative study in intensive care units in England and Israel.
To explore factors perceived to contribute to 'a good death' and the quality of end of life care in two countries with differing legal and cultural contexts. Multi-centre study consisting of focus group and individual interviews with intensive care nurses. Data were analysed using qualitative thematic analysis; emotional content was analysed using specialist linguistic software. Fifty five Registered Nurses in intensive care units in Israel (n=4) and England (n=3), purposively sampled across age, ICU experience and seniority. Four themes and eleven sub-themes were identified that were similar in both countries. Participants identified themes of: (i) timing of communication, (ii) accommodating individual behaviours, (iii) appropriate care environment and (iv) achieving closure, which they perceive prevent, and contribute to, a good death and good quality of end of life care. Emotional content showed significant amount of 'sadness talk' and 'discrepancy talk', using words such as 'could and 'should' when participants were talking about the actions of clinicians. The qualities of a good death were more similar than different across cultures and legal systems. Themes identified by participants may provide a framework for guiding end of life discussions in the intensive care unit.


Surveillance imaging of grade 1 astrocytomas in children: can duration and frequency of follow-up imaging and the use of contrast agents be reduced?
The optimum strategy for the surveillance of low-grade gliomas in children has not been established, and there is concern about the use of gadolinium-based contrast agents (GBCAs), particularly in children, due to their deposition in the brain. The number of surveillance scans and the use of GBCAs in surveillance of low-risk tumours should ideally be limited. We aimed to investigate the consistency and utility of our surveillance imaging and also determine to what extent the use of GBCAs contributed to decisions to escalate treatment in children with grade 1 astrocytomas. This was a retrospective single-centre study at a tertiary paediatric hospital. All children with a new diagnosis of a non-syndromic World Health Organization (WHO) grade 1 astrocytoma between 2007 and 2013 were included, with surveillance imaging up to December 2018 included in analysis. The intervals of surveillance imaging were recorded, and imaging and electronic health records were examined for decisions related to treatment escalation. Eighty-eight patients had 690 surveillance scans in the study period. Thirty-one patients had recurrence or progression leading to treatment escalation, 30 of whom were identified on surveillance imaging. The use of GBCAs did not appear to contribute to multidisciplinary team (MDT) decisions in the majority of cases. Surveillance imaging could be reduced in number and duration for completely resected cerebellar tumours. MDT decisions were rarely made on the basis of post-contrast imaging, and GBCA administration could therefore potentially be restricted in the setting of surveillance of grade 1 astrocytomas in children.


Functional dysconnectivity within the emotion-regulating system is associated with affective symptoms in major depressive disorder: A resting-state fMRI study.
Major depressive disorder (MDD) can be characterized as a multidimensional and system-level disorder. The neuropathophysiological abnormalities have been reported to be distributed in emotion regulation system, involving the prefrontal cortex (PFC), limbic and striatum in convergent studies. Decrease of positive affect and increase of negative affect are recognized as a hallmark of MDD. However, the dysfunctions in affective processing in MDD within the emotion regulation system remains largely unclear. In this study, our goals are to characterize the dysconnectivity pattern within this system and explore the relationships between this kind of dysconnectivity pattern and affective symptoms, which might help us better look into the neuropathophysiological mechanisms underlying MDD. A total of 34 MDD and 34 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rsfMRI). The alterations in functional connectivity (FC) within the emotion regulation system and their relationships with affective symptoms were explored. Compared with HCs, MDD patients showed aberrant FC within this system. Importantly, deceased FC was mainly involved in the prefrontal-limbic system, while elevated FC was observed in the prefrontal-striatum system. In the MDD group, decreased FC of right posterior hippocampus-left dorsolateral prefrontal cortex (dlPFC) was negatively associated with the negative affect scores and Hamilton Depression Rating Scale scores and the FC of left ventral striatum-left dlPFC was significantly negatively related with the positive affect scores. These findings demonstrated that MDD showed characteristic pathological alterations of the emotion regulation system. Dysconnectivity within prefrontal-limbic system might be more related to the dysregulation of negative affect, whereas dysconnectivity within prefrontal-striatum system might influence more on positive affect processing. The decrease in positive affect and increase in negative affect in MDD might have different pathological basis. These results could help better understand the dysconnectivity pattern in the emotion-regulating system underlying depression.


In hypertension, the kidney breaks your heart.
The renin-angiotensin system (RAS) is a master regulator of blood pressure and fluid homeostasis. Because RAS components are expressed in several tissues that may influence blood pressure, studies using conventional gene targeting to globally interrupt the RAS have not determined the contributions of angiotensin II receptor type 1 (AT(1)) receptors in specific tissue pools to blood pressure regulation and tissue injury. Recent experiments using kidney cross-transplantation and mice lacking the dominant murine AT(1) receptor isoform, AT(1A), have demonstrated that 1) AT(1) receptors inside and outside the kidney make equivalent contributions to normal blood pressure homeostasis, 2) activation of renal AT(1) receptors is required for the development of angiotensin II-dependent hypertension, and 3) this blood pressure elevation rather than activation of AT(1) receptors in the heart drives angiotensin II-induced cardiac hypertrophy. These findings, together with previous experiments, confirm the kidney's critical role in the pathogenesis of hypertension and its complications.


Homogeneous chicken heart mitochondrial creatine kinase purified by dye-ligand and transition-state analog-affinity chromatography.
A method for the preparation of homogeneous mitochondrial creatine kinase from chicken heart is presented. The two-column procedure, which can be completed in 2 days, uses Procion red dye and transition-state analog-affinity chromatography. The transition-state analog-affinity chromatographic system utilizes an ADP-hexane-agarose column in conjunction with the transition-state analog complex originally developed by E. J. Milner-White and D. C. Watts (1971, Biochem, J. 122, 727-740) composed of KNO3, MgCl2, creatine, and ADP. The enzyme is a dimer composed of 2 Mr 43,000 subunits. The sequence of the first N-terminal 20 amino acids shows that the enzyme is different from the cytosolic isozymes but similar to human mitochondrial creatine kinase. The enzyme has an extinction coefficient of epsilon 280 nm = 2.22 +/- 0.10 ml X mg-1 X cm-1 and a maximum velocity of 200 IU/ml at pH 7.0. The kinetic constants for the chicken heart mitochondrial isozyme are comparable to values for the canine and human heart isozyme.


Design of a compact tuning fork-shaped notched ultrawideband antenna for wireless communication application.
A new compact planar notched ultrawideband (UWB) antenna is designed for wireless communication application. The proposed antenna has a compact size of 0.182λ × 0.228λ × 0.018λ where λ is the wavelength of the lowest operating frequency. The antenna is comprised of rectangular radiating patch, ground plane, and an arc-shaped strip in between radiating patch and feed line. By introducing a new Tuning Fork-shaped notch in the radiating plane, a stopband is obtained. The antenna is tested and measured. The measured result indicated that fabricated antenna has achieved a wide bandwidth of 4.33-13.8 GHz (at -10 dB return loss) with a rejection frequency band of 5.28-6.97 GHz (WiMAX, WLAN, and C-band). The effects of the parameters of the antenna are discussed. The experiment results demonstrate that the proposed antenna can well meet the requirement for the UWB communication in spite of its compactness and small size.


Leptospira interrogans serotype pomona in Saskatchewan: isolation from a naturally infected striped skunk.
Leptospira interrogans serotype pomona was isolated from the kidneys of a normal striped skunk (Mephitis mephitis hudsonicus) collected near Kindersley, Saskatchewan. Although there were no gross lesions, small foci of chronic interstitial nephritis were observed microscopically. This is the first reported isolation of serotype pomona for the prairie provinces.


Progress of unrelated bone marrow donor search at the University Hospital of Essen (1991-1994).
The development of unrelated bone marrow donor search (UMDS) was analyzed in a retrospective single-center study covering the period from 1991 to 1994. The data files of the 285 enrolled UMDS patients were evaluated for the patients' underlying disease, HLA phenotype frequency, year of search start, UMDS duration/outcome, and the origin of identified donors. Within 3 months after UMDS start, a donor was found in 5%, 10%, 19%, and 49% of the searches started in 1991 (n = 57), 1992 (n = 73), 1993 (n = 77), and 1994 (n = 78, until September), respectively. The total UMDS success rate increased from 53% (1991 group) to 67% (1994 group), with 5% and 54%, respectively, of the accepted donors being supplied by German registries. Thus, the current UMDS procedure provides a suitable donor for the majority of the patients lacking a related donor, and the majority of the donors are now facilitated by national donor centers.


Requirements of supply chain management in differentiating European pork chains.
This paper summarizes results obtained by research into pork chain management in the EU Integrated Project Q-Porkchains. Changing demands for intrinsic and extrinsic quality attributes of pork products impact the way supply chain management should be organized from the farmer down to the consumer. The paper shows the importance of Quality Management Systems for integrating supply chains and enhancing consumer confidence. The paper also presents innovations in information system integration for aligning information exchange in the supply chain and logistics concepts based on innovative measurement technologies at the slaughterhouse stage. In the final section research challenges towards sustainable pork supply chains satisfying current consumer demands are presented.


Acceptance, panic, and partial recovery the pattern of usage of drug-eluting stents after introduction in the U.S. (a report from the American College of Cardiology/National Cardiovascular Data Registry).
Review the use of drug-eluting stents (DES) to evaluate changes in use. The DES were approved after several small studies in carefully selected patients showed dramatic reduction in in-stent restenosis. The DES were then rapidly adopted into routine practice. In 2006, 3 years after introduction, serious concerns regarding long-term safety were raised. We queried the American College of Cardiology/National Cardiovascular Data Registry (ACC/NCDR) CathPCI Registry. The percentage of DES used through mid-2009 was reviewed overall and in subgroups of patients categorized by lesion type, clinical factors, insurance, and hospital characteristics. Multivariable logistic models relating these covariates to DES usage were constructed for 3 relevant time intervals. A total of 2,247,647 coronary stent procedures were analyzed. By 2005 over 90% of first stents placed were DES. Safety concerns arising in 2006 reduced DES use to 64% of first stent placed. After publication of salutary outcomes data in 2008, usage increased to 76% by mid-2009. The logistic models demonstrated decreased likelihood of DES usage in patients with: 1) ST-segment elevation myocardial infarctions; and 2) no medical insurance. The DES usage increased for in-stent restenosis. Hospital characteristics were not associated with significant differences in DES usage. There was rapid adoption of DES into U.S. clinical practice. Concern for late stent thrombosis in 2006 significantly altered DES use with reductions seen in subgroups at risk for thrombosis and patients with no insurance. These rapid cyclic changes after DES introduction reinforce the need for continuous, timely reporting of outcomes data after the introduction of new technologies.


Modeling and prediction of COVID-19 pandemic using Gaussian mixture model.
COVID-19 is caused by a novel coronavirus and has played havoc on many countries across the globe. A majority of the world population is now living in a restricted environment for more than a month with minimal economic activities, to prevent exposure to this highly infectious disease. Medical professionals are going through a stressful period while trying to save the larger population. In this paper, we develop two different models to capture the trend of a number of cases and also predict the cases in the days to come, so that appropriate preparations can be made to fight this disease. The first one is a mathematical model accounting for various parameters relating to the spread of the virus, while the second one is a non-parametric model based on the Fourier decomposition method (FDM), fitted on the available data. The study is performed for various countries, but detailed results are provided for the India, Italy, and United States of America (USA). The turnaround dates for the trend of infected cases are estimated. The end-dates are also predicted and are found to agree well with a very popular study based on the classic susceptible-infected-recovered (SIR) model. Worldwide, the total number of expected cases and deaths are 12.7 × 106 and 5.27 × 105, respectively, predicted with data as of 06-06-2020 and 95% confidence intervals. The proposed study produces promising results with the potential to serve as a good complement to existing methods for continuous predictive monitoring of the COVID-19 pandemic.


Interaction of Listeria monocytogenes autolysin amidase with glycosaminoglycans promotes listerial adhesion to mouse hepatocytes.
Adherence to the cell surface is a key event during infection of pathogenic microorganisms. We have previously reported that autolysin amidase (Ami) of Listeria monocytogenes promotes an efficient listerial adherence to mouse hepatocytes and requires for listerial pathogenicity. Cell wall anchoring (CWA) domain of Ami has been shown to bind lipoteichoic acid on listerial cell wall but the binding of Ami to host cell surface molecules remains to be determined. In this study, we present evidence here that Ami promotes efficient adherence of L. monocytogenes to mouse hepatocytes mediated by glycosaminoglycans (GAGs). The adhesion of L. monocytogenes wild type but not Ami-deficient mutant to the hepatocytes was dramatically attenuated by 4-nitrophenyl-β-D-xylopyranoside, a specific inhibitor of GAG association to cell surface. Full-length and truncated Ami were used to investigate the binding of Ami to GAGs and we found that four-repeated CWA of Ami is sufficient to bind GAGs on the host cell surface. Competitive assay and surface plasmon resonance demonstrated that Ami interacts with sulfated GAGs but not non-sulfated GAGs. The results suggest that Ami acts as an adhesin of L. monocytogenes to hepatocytes by interaction via its four-repeated CWA domain and sulfated GAGs.


Predicting hospitalization in children with acute asthma.
Acute asthma is one of the most common medical emergencies in children. Appropriate assessment/treatment and early identification of factors that predict hospitalization are critical for the effective utilization of emergency services. To identify risk factors that predict hospitalization and to compare the concordance of the Modified Pulmonary Index Score (MPIS) with the Global Initiative for Asthma (GINA) guideline criteria in terms of attack severity. The study population was composed of children aged 5-18 years who presented to the Emergency Departments (ED) of the tertiary reference centers of the country within a period of 3 months. Patients were evaluated at the initial presentation and the 1(st) and 4(th) hours. Of the 304 patients (median age: 8.0 years [interquartile range: 6.5-9.7]), 51.3% and 19.4% required oral corticosteroids (OCS) and hospitalization, respectively. Attack severity and MPIS were found as predicting factors for hospitalization, but none of the demographic characteristics collected predicted OCS use or hospitalization. Hospitalization status at the 1(st) hour with moderate/severe attack severity showed a sensitivity of 44.1%, specificity of 82.9%, positive predictive value of 38.2%, and negative predictive value of 86.0%; for MPIS ≥ 5, these values were 42.4%, 85.3%, 41.0%, and 86.0%, respectively. Concordance in prediction of hospitalization between the MPIS and the GINA guideline was found to be moderate at the 1(st) hour (κ = 0.577). Attack severity is a predictive factor for hospitalization in children with acute asthma. Determining attack severity with MPIS and a cut-off value ≥ 5 at the 1(st) hour may help physicians in EDs. Having fewer variables and the ability to calculate a numeric value with MPIS makes it an easy and useful tool in clinical practice.


Treatment of neuroblastoma stage 4 with 131I-meta-iodo-benzylguanidine, high-dose chemotherapy and immunotherapy. A pilot study.
Disseminated neuroblastoma after infancy has a prognosis of approximately 10-20% with conventional therapy. We investigated the role of high-dose chemotherapy (HDCT) with peripheral blood stem cell (PBSC) rescue in combination with 131I-metaiodobenzylguanidine ([131I-m]IBG). 11 children with neuroblastoma stage 4 were pretreated within the German Neuroblastoma Trial NB90 and included in a high-dose concept for consolidation. Remission was documented by ultrasound, CT, NMR, or [123I-m]IBG scanning. HDCT was a combination of melphalan (180 mg/m2), carboplatin (1,500 mg/m2) and etoposide (40 mg/kg). All children were treated by [131I-m]IBG (0.58 GBq/kg) prior to high-dose treatment. All 11 children were additionally treated with antiGD2 murine- or chimeric-antibody (ch14.18). 4 children had no change to their remission status but three achieved a complete response (from a partial response to first line) and one a partial response (from no response to first line). The other 3 children progressed, 2 dying of their disease. Using Kaplan-Meier analysis, the probability of progression-free survival was 0.70 +/- 0.15 with a median observation time of 19 months. 9/11 children are alive, 8 without progression or relapse, whilst 2 have died of their disease. The combination of mIBG plus high-dose chemotherapy with PBSC support supplemented by immunotherapy with antiGD2 antibody appears to be a feasible and effective treatment regimen for disseminated neuroblastoma in this limited series. Larger numbers of patients should be treated to confirm these results.


Therapeutic options for 5-lipoxygenase inhibitors.
5-Lipoxygenase (5-LO) catalyzes the conversion of arachidonic acid (AA) into leukotriene (LT) A(4) and 5-hydroperoxyeicosatetraenoic acid. LTA(4) can then be converted into LTB(4) by LTA(4) hydrolase or into LTC(4) by LTC(4) synthase and the LTC(4) synthase isoenzymes MGST2 and MGST3. LTB(4) is a potent chemoattractant for neutrophils, eosinophils and monocytes leading to adherence of phagocytes to vessel walls, neutrophil degranulation and release of superoxide anions. LTC(4) and its metabolite, LTD(4), are potent bronchoconstrictors that increase vascular permeability and stimulate mucus secretion from airways. Recent data also suggest that LT have an immunomodulatory role. Due to these properties, the increased biosynthesis of LT in asthma, and based upon clinical data obtained with CysLT(1) receptor antagonists in asthma patients, there is a consensus that CysLT play a prominent role in asthma. In this review, we summarize the knowledge on possible functions of the 5-LO pathway in various diseases like asthma, cancer and cardiovascular events and review the corresponding potential therapeutic roles of 5-LO inhibitors.


Comparison of speaking fundamental frequency between premenopausal women and postmenopausal women with and without hormone therapy.
The purpose of this study was to investigate the speaking fundamental frequency (SFF) in pre- and postmenopausal women with and without hormone therapy (HT) and with low and high body mass index (BMI). The SFF of premenopausal women with low BMI (n = 22) was compared with the SFF of premenopausal women with high BMI (n = 13), postmenopausal women with HT and low BMI (n = 35), postmenopausal women with HT and high BMI (n = 19), postmenopausal women without HT and with low BMI (n = 28) and postmenopausal women without HT and with high BMI (n = 12) using ANCOVA and post hoc tests. A significantly lower SFF of the voice was only found in postmenopausal women without HT and with a low BMI. The results of this study suggest that the menopause lowers the voice with approximately 14 Hz and that HT and adipose tissue (high BMI) might counteract the menopausal drop in SFF.


Methylation tolerance in mismatch repair proficient cells with low MSH2 protein level.
Loss of DNA mismatch repair has been found in tumors associated with the familial cancer predisposition syndrome HNPCC (hereditary non-polyposis colorectal cancer) and a subset of sporadic cancers. MSH2 deficiency abolishes the action of the mismatch repair system, resulting in a phenotype which is characterized by an increased accumulation of base substitutions and frameshifts, enhanced recombination between homologous but non-identical DNA sequences, and tolerance to the cytotoxic effects of methylating agents. In this study we describe an embryonic stem cell line in which the level of MSH2 protein is 10-fold reduced compared to that in wild-type cells. Remarkably, these MSH2-low cells were as resistant to killing by methylating agents as cells completely lacking MSH2, while they had retained almost maximal mismatch repair capacity as judged from their anti-mutagenic and anti-recombinogenic capacity and the absence of microsatellite instability. In contrast, MSH2-low cells were highly sensitive to methylation-damage induced mutagenesis. Thus, 10-fold reduced MSH2 protein levels render cells resistant to the toxic and highly sensitive to the mutagenic effects of methylating agents. This condition is not manifested by microsatellite instability and may have implications for both the etiology and treatment of cancer.


Multi-modal quantitative MRI investigation of brain tissue neurodegeneration in multiple sclerosis.
To investigate the utility of multimodal quantitative MRI (qMRI) and atlas-based methods to identify characteristics of lesion-driven injury and neurodegeneration in relapsing remitting multiple sclerosis (RRMS). This work is health insurance portability and accountability act compliant. High resolution T1-weighted, dual echo, and fluid-attenuated inversion recovery and diffusion tensor MRI images were prospectively acquired on 68 RRMS patients (range, 25-58 years) and 68 age-matched controls. The data were analyzed using standardized human brain atlas-based tissue segmentation procedures to obtain regional volumes and their corresponding T2 relaxation times and DTI maps. Group-averaged brain atlas-based qMRI maps of T2, fractional anisotropy and diffusivities are visually presented and compared between controls and RRMS. The analysis shows a widespread injury in RRMS. Atrophy of the corpus callosum (CC) was substantial in RRMS. The qMRI attributes of the neocortex in combination with the CC such as T2 and diffusivities were elevated and correlated with disability. Using a standardized multimodal qMRI acquisition and analyses that accounted for lesion distribution we demonstrate that cerebral pathology is widespread in RRMS. Our analysis of CC and neocortex qMRI metrics in relation to disability points to a neurodegenerative injury component that is independent from lesions.


Choline deficiency and chemical carcinogenesis.
We have reviewed the current status of our knowledge concerning the biologic effects of dietary choline (lipotrope) deficiency in modifying chemical carcinogenesis in experimental animals and discussed its possible mechanisms. Choline deficiency produces various pathologic lesions, involving virtually every organ of the body, as a result of a decrease in phospholipid and acetylcholine synthesis and in the supply of labile methyl groups. The liver is the only organ in which a relationship has been consistently demonstrated between choline deficiency and chemically induced tumors. The deficient diet enhances the initiating potency of several carcinogens and acts as a strong cocarcinogen. Diet also exerts a strong promoting effect, though the possibility that it is a complete carcinogen cannot be ruled out. Phase I enzymes of the carcinogen metabolizing system are uniformly depressed by choline deficiency, but very little information is available regarding the effects of diet on Phase II enzymes that detoxify carcinogen metabolites. Possible modifications of carcinogen-induced DNA damage and their repair processes have not been adequately scrutinized. Solid evidence suggests that feeding a choline-deficient diet leads to enhanced liver cell proliferation, an inadequate supply of methyl groups for transmethylation reactions, and membrane lipid peroxidation. Induced cell proliferation and hypomethylation of DNA may alter the state of gene expression, including that of specific cellular oncogenes. Lipid peroxidation may alter the structure and function of membrane receptors related to liver cell growth or may directly damage cellular DNA. Thus these alterations, individually or in combination, could play a critical role in the diet-induced modification of chemical carcinogenesis.


Influence of ACTH-(1-24) on metabolic acidosis and hypoxemia induced by massive hemorrhage in rats.
In anesthetized rats, step-wise bleeding to a severe condition of hemorrhagic shock causes a decrease in arterial and venous pH and in venous PO2 and SO2 and an increase in arterial PO2 and in venous PCO2 and lactic acid. The intravenous bolus injection of ACTH-(1-24) (160 micrograms/kg)--which causes a rapid and sustained reversal of the shock condition--produces a gradual and almost complete recovery (within 60 min) of venous PO2, PCO2 and SO2; on the other hand, the normalization of blood pH and lactate is preceded by a further worsening during the first minutes after treatment. On the whole, these data are compatible with the ACTH-(1-24)-induced mobilization of the residual blood--which is pooled in poorly oxygenated tissues--and with the improved circulatory and respiratory functions.


Direct stenting with a combined intravascular ultrasound-coronary stent delivery platform: a feasibility trial.
IVUS is considered as the most accurate tool for the assessment of optimal stent deployment. Direct stenting has shown to be a safe, efficient, and resource-saving procedure in selected patients. In a prospective 1-month feasibility trial, a new combined IVUS-coronary stent delivery platform (Josonics Flex, Jomed, Helsingborn, Sweden) was evaluated during direct stenting in consecutive patients considered eligible for direct stenting. The feasibility endpoint was successful stent deployment without any clinical adverse event, while the efficacy endpoint was strategic adaptation according to standard IVUS criteria for optimal stent deployment at the intermediate phase (after a result considered angiographically optimal) and at the end of the intervention (after optimization according to IVUS standards). A total of 16 patients were successfully treated with this device without any major clinical complication. At the intermediate phase, optimal stent deployment was achieved in four patients only, while at the end only one patient had nonoptimal IVUS stent deployment. In particular, the minimal in-stent cross-section area increased from 6.3 +/- 1.2 to 8.3 +/- 2.5 mm(2). These preliminary data demonstrate the feasibility of direct stenting with a combined IVUS-stent catheter in selected patients and confirm the results from larger randomized trials on the impact of IVUS on strategic adaptations during coronary stent placement.


Effects of prostaglandin E1 on callus formation in rabbits.
Recent research has focused on identifying chemical modulators of osteogenesis. We present initial findings on the osteoinductive properties of prostaglandin Е1 (Vasaprostan), using a rabbit model. Data were collected on callus formation in 14 male rabbits. These were divided into two groups (control and treatment) with 7 animals in each group. In all animals, the right tibia was fractured using a standardized protocol and stabilized by an intramedullary nail. Treatment group received a 5 μg/kg subcutaneous injection of PGE1/day during 10 postoperative days. Visual and radiological evaluation of callus formation was prospectively collected. After 30 days, all animals were killed and the tibia specimens were examined histologically. In all the treatment group animals, fractures were consolidated radiologically by day 30. No treatment group animals and two control group animals were excluded form the experiment. In the control group, 4 animals demonstrated slower callus formation than the main group. Two control group animals were excluded from the experiment on the 20th day due to wound infection; one developed a nonunion. The mean coefficient of bone callus thickening in the main group was 2.08 (±0, 16) and 1.77 (±0.05) (p < 0.05) in the control group. Calculation of mean quantity of neogenic vessels in 10 random visual fields of the bone callus revealed 78 (±9.82) in the main group and 40 (±4.68) in the control group (p < 0.05). Our study demonstrates an increased rate and amount of bone callus formation in the group treated with prostaglandin E1 compared to the control group. Prospective radiological analysis was corroborated by histologic evaluation.


A 13-Year National Monitoring Study to Assess Narcotic Prescriptions and Indications (2007-2019).
Analgesics are among the most widely used drugs worldwide. This study describes the population treated with narcotic analgesics, their therapeutic indications and how the data have evolved over a decade. A cross-sectional, national, multicentre survey study was conducted that included surveys taken every year from 2007 to 2019 in a national sample of 1500 randomly selected dispensing pharmacies. The mean age of patients, mostly women (around 60%), remained stable over the study period (63.2 ± 17.1 years in 2007, 68.2 ± 17.2 years in 2019). The proportion of patients treated for more than 3 months increased from 2007 to 2019. Most prescriptions involved morphine, oxycodone and fentanyl (98.5% of all prescriptions in 2019). Morphine prescriptions dropped dramatically from 49.6% (2007) to 32.3% (2019) of the total narcotic analgesics. Fentanyl prescriptions varied from 40.1% in 2007 to 32.2% in 2019. Prescriptions of oxycodone, regardless of the indication, increased steadily from 2007, from 8.3 to 34% in 2019, becoming the most prescribed narcotic analgesic for the first time since the beginning of the survey. This study demonstrates how narcotic opioids are prescribed, thanks to the active participation of health professionals, and confirms the striking increase in the prescription of oxycodone.


Microarray scanner calibration curves: characteristics and implications.
Microarray-based measurement of mRNA abundance assumes a linear relationship between the fluorescence intensity and the dye concentration. In reality, however, the calibration curve can be nonlinear. By scanning a microarray scanner calibration slide containing known concentrations of fluorescent dyes under 18 PMT gains, we were able to evaluate the differences in calibration characteristics of Cy5 and Cy3. First, the calibration curve for the same dye under the same PMT gain is nonlinear at both the high and low intensity ends. Second, the degree of nonlinearity of the calibration curve depends on the PMT gain. Third, the two PMTs (for Cy5 and Cy3) behave differently even under the same gain. Fourth, the background intensity for the Cy3 channel is higher than that for the Cy5 channel. The impact of such characteristics on the accuracy and reproducibility of measured mRNA abundance and the calculated ratios was demonstrated. Combined with simulation results, we provided explanations to the existence of ratio underestimation, intensity-dependence of ratio bias, and anti-correlation of ratios in dye-swap replicates. We further demonstrated that although Lowess normalization effectively eliminates the intensity-dependence of ratio bias, the systematic deviation from true ratios largely remained. A method of calculating ratios based on concentrations estimated from the calibration curves was proposed for correcting ratio bias. It is preferable to scan microarray slides at fixed, optimal gain settings under which the linearity between concentration and intensity is maximized. Although normalization methods improve reproducibility of microarray measurements, they appear less effective in improving accuracy.


Thirty-six cases of obturator hernia: does computed tomography contribute to postoperative outcome?
Obturator hernia is relatively rare and occurs mostly in elderly, thin, multiparous women. Recent reports have highlighted the importance of pelvic computed tomography (CT) for the preoperative diagnosis. Thirty-six patients with an obturator hernia operated in our hospital were divided retrospectively into two groups (group A: 18 operations from 1973 to 1986, before we used CT; group B: 18 CT cases from 1987 to 1995). Preoperative diagnoses, operative procedures, and postoperative course were reviewed. No statistically significant differences were found between groups A and B in terms of patient characteristics. Rates of accurate preoperative diagnoses were significantly higher in group B: 39% (7/18) in group A and 78% (14/18) in group B (p = 0.018). The intraoperative findings, occurrence of postoperative complications, and overall mortality rates were similar between the two groups. There were four postoperative deaths (mortality rate 11%). Three of four patients who died had panperitonitis because of small bowel perforation. The correct preoperative diagnosis of obturator hernia was facilitated by CT of the pelvis, but it has no impact on patient outcome. Early diagnosis and surgical intervention are essential for this rare entity.


A Novel Method for Preoperative Positioning of Total Ankle Replacement Using 3D Digital Model.
To establish a digital model of the ankle joint through 3D imaging technology and explore the preoperative placement of ankle replacement prostheses. Computed tomography images of intact ankle joints from 54 cases in the outpatient and inpatient departments of our hospital were collected; according to the INBONE® total ankle system surgery process, the surgery model and surgical osteotomy were finished using MIMICS based on computer simulation method. The shortest distance was measured between the center point and the anterior, posterior, medial, and lateral, respectively, to ensure the precise position of the ankle replacement prosthesis by digital simulation surgery. The relationship between the two variables was analyzed by bivariate correlation analysis. The dataset of this study included 48 cases of the sub-data set (26 males and 22 females) and included 27 cases of left ankle and 21 cases of right ankle. The average medial malleolar angle was 18.67°± 2.87°, the average amount of bone resection was 12.13 ± 1.86 cm3 , the mid-anterior distance was 1.72 ± 0.19 cm, the mid-posterior distance was 2.00 ± 0.19 cm, the ratio of mid-anterior to mid-posterior was 0.87, the mid-medial distance was 1.26 ± 0.17 cm, the mid-lateral distance was 1.19 ± 0.16 cm, and the ratio of mid-medial to mid-lateral was 1.06. After osteotomy, the anteroposterior diameter was 3.73 ± 0.32 cm, the transverse diameter was 2.46 ± 0.27 cm, and the ratio of anteroposterior diameter to transverse diameter was 1.53. In the bottom view, the shape after osteotomy is rectangular. The mid-anterior distance was strongly negatively correlated with age, the mid-anterior distance and the amount of bone resection, the mid-medial distance and the amount of bone resection, the mid-lateral distance and the amount of bone resection, the mid-lateral distance and the anteroposterior diameter, the anteroposterior diameter and the transverse diameter were all strongly positively correlated. The projection point of the lower tibia centerline on the tibial horizontal osteotomy surface is located at a position slightly anterior to the midpoint of the transverse diameter after ankle arthroplasty. The rational positioning of the total ankle replacement is located at both a position slightly anterior to the midpoint of the transverse diameter and midpoint of the anteroposterior diameter, which can be used as a reference method before total ankle arthroplasty surgery.


Partitioning behavior and stabilization of hydrophobically coated HfO2, ZrO2 and Hfx Zr 1-x O2 nanoparticles with natural organic matter reveal differences dependent on crystal structure.
The interactions of engineered nanomaterials with natural organic matter (NOM) exert a profound influence on the mobilities of the former in the environment. However, the influence of specific nanomaterial structural characteristics on the partitioning and colloidal stabilization of engineered nanomaterials in various ecological compartments remains underexplored. Herein, we present a systematic study of the interactions of humic acid (HA, as a model for NOM) with monodisperse, well-characterized, ligand-passivated HfO(2), ZrO(2), and solid-solution Hf(x)Zr(1-x)O(2) nanoparticles (NPs). We note that mixing with HA induces the almost complete phase transfer of hydrophobically coated monoclinic metal oxide (MO) NPs from hexane to water. Furthermore, HA is seen to impart appreciable colloidal stabilization to the NPs in the aqueous phase. In contrast, phase transfer and aqueous-phase colloidal stabilization has not been observed for tetragonal MO-NPs. A mechanistic model for the phase transfer and aqueous dispersal of MO-NPs is proposed on the basis of evidence from transmission electron microscopy, ζ-potential measurements, dynamic light scattering, Raman and infrared spectroscopies, elemental analysis, and systematic experiments on a closely related set of MO-NPs with varying composition and crystal structure. The data indicate the synergistic role of over-coating (micellar), ligand substitution (coordinative), and electrostatic processes wherein HA acts both as an amphiphilic molecule and a charged chelating ligand. The strong observed preference for the phase transfer of monoclinic instead of tetragonal NPs indicates the importance of the preferential binding of HA to specific crystallographic facets and suggests the possibility of being able to design NPs to minimize their mobilities in the aquatic environment.


Effect of telemonitoring on self-care behaviors among community-dwelling adults with heart failure: a quantitative systematic review protocol.
This systematic review seeks to synthesize evidence to determine the effect of telemonitoring on self-care behaviors of adults with heart failure. There is a high-level body of evidence demonstrating that telemonitoring is an appropriate and effective therapy for many chronic conditions and, specifically, for patients with heart failure. However, the effect of telemonitoring on self-care behaviors in the adult population with heart failure is unknown. This review will include studies on adult participants (18 years and over) diagnosed with heart failure who use telemonitoring in the ambulatory setting. Studies of pediatric heart failure patients, and adult heart failure patients in acute care settings or in a care facility, will be excluded. The search for studies will include English language studies published from 1997. Search terms will include heart failure, telemonitoring, self-care, and outpatient/ambulatory care, and will be used in three key sources: CINAHL, Embase, and PubMed. For the full review, Epistomonikos, ProQuest, PsycINFO, and Web of Science will also be searched. Using inclusion/exclusion criteria, two reviewers will select studies based on a three-step process. Methodological quality will be determined using critical appraisal checklists appropriate to the study design. Data extraction will include populations, study designs and methods, interventions, and outcomes related to self-care behaviors. Pooled studies will allow calculation of meta-analysis, while calculated effect sizes and confidence intervals will inform impact and precision of effect. PROSPERO CRD42019131852.


I am one of you! Team prototypicality as a facilitator for female leaders.
In the present study, we complement role congruity theory with insights from the Social Identity Model of Leadership. We propose that especially female leaders benefit from team prototypicality, i.e., being representative of the group they are leading. We assume that team prototypicality shifts the comparative frame away from higher-order categories like gender and leader roles to more concrete team-related properties and thereby reduces disadvantages for female leader that stem from the incongruity between the leader role and the female gender role stereotypes. Further, this effect should affect both (female) leaders themselves and their perception by their followers. Building on previous research, we predict, first, lower authentic leadership behavior for female than male leaders. Second, that team prototypicality positively relates to authentic leadership and trust in leader. Third, that team prototypicality has stronger relations to authentic leadership and trust in leader for female compared to male leaders. We tested assumptions in a randomized online experiment (Study 1, N = 315) and a cross-sectional survey study (Study 2, N = 300). We did not find consistent support for the assumed gender differences in authentic leadership. But our results (both in manifest and in latent analyses) show that team prototypicality-both self-perceived (Study 1) and as perceived by employees (Study 2)-is related to more authentic leadership and more trust in leader (Study 2) and that these relations are stronger for female than for male leaders. Furthermore, we tested in Study 2 an extended model including follower's job satisfaction as the final follower outcome affected via team prototypicality, leader gender, authentic leadership, and trust in leader. Thereby, we found that team prototypicality has direct and indirect effects on job satisfaction as carried through authentic leadership and trust in leader, respectively. Together, the results of both studies support our assumptions and show that female leaders can reduce role incongruity barriers through high team prototypicality. Implications for future research and practical implications of these results for gender equality are discussed.


Design, synthesis and anti-cancer activity evaluation of podophyllotoxin-norcantharidin hybrid drugs.
In this study, we designed and synthesized eighteen podophyllotoxin-norcantharidin hybrid drugs which could exhibit more potent anti-cancer activity than the parent drugs. Through the anti-proliferation assay, the most potent anti-cancer agent was screened out, namely Q9 (IC50=0.88±0.18μM against MCF-7 cell line), and it showed lower cytotoxicity against non-cancer cells, human embryonic kidney cells (293T) (IC50=54.38±3.78μM). Additionally, based on the flow cytometry analysis result, it can cause a remarkable cell cycle arrest at G2/M phase and induce apoptosis in MCF-7 cells more significantly than podophyllotoxin or norcantharidin per se. Moreover, the expression of cell cycle relative protein CDK1 was up regulated while a protein required for mitotic initiation, Cyclin B1 was down regulated. Furthermore, according to the confocal microscopy observation results, it was shown that Q9 was a potent tubulin polymerization inhibitor and the effect is comparable to that of colchicine. For further investigation on the aforementioned mechanisms, we performed western blot experiments, thus finding the increase of the cleavage of PARP. Consistent with these new findings, molecular docking observations suggested that compound Q9 could be developed as a potential anticancer agent.


Mechanism for the coupling of ATP hydrolysis to the conversion of 5-formyltetrahydrofolate to 5,10-methenyltetrahydrofolate.
5,10-Methenyltetrahydrofolate synthetase catalyzes the irreversible conversion of 5-formyl-tetrahydropteroylpolyglutamates (5-CHO-H4PteGlu(n)) to 5,10-methenyltetrahydropteroylpolyglutamates (5, 10-CH(+)-H4PteGlu(n)). The equilibrium of the nonenzymatic reaction, which equilibrates slowly in the absence of enzyme, greatly favors 5-CHO-H4PteGlu(n). The enzyme couples the reaction to the hydrolysis of ATP shifting the equilibrium to favor 5,10-CH(+)-H4PteGlu(n). Substrate-dependent non-equilibrium isotope exchange of [3H]ADP into ATP was observed, suggesting the formation of a phosphorylated intermediate of 5-CHO-H4PteGlu(n) during the enzyme-catalyzed reaction. The competitive inhibitor 5-formyltetrahydrohomofolate also supported the ADP to ATP exchange, suggesting that this molecule could also form a phosphorylated intermediate. The initial rates of the ADP-ATP exchange with saturating ADP were about 70 s-1 for both compounds, while the kcat values for product formation were 5 s-1 for 5-CHO-H4PteGlu(n) and 0.005 s-1 for 5-formyltetrahydrohomofolate. Starting with 5(-)[18O]CHO-H4PteGlu(n), it was shown by 31P NMR that the formyl oxygen of the substrate was transferred to the product phosphate during the reaction. This further supports the existence of a phosphorylated intermediate. The formyl group of 5-CHO-H4PteGlu(n) is known to be an equilibrium mixture of two rotamers. Stopped-flow analysis of the enzymatic reaction showed that only one of the rotamers serves as a substrate for the enzyme.


Clearance of diesel soot particles from rat lung after a subchronic diesel exhaust exposure.
The particulate exhaust of diesel engines consists of 0.1--0.2 micrometers mass median diameter particles composed of a carbonaceous core and adsorbed organic compounds. A technique was needed to determine accumulated lung burdens of particles in animals exposed to diesel exhaust as a determinant of dose. A method was developed for determining lung burdens of diesel soot particles in rats at 1 day, and at 1, 5, 15, 33 and 52 weeks after cessation of a subchronic exposure to diluted diesel exhaust. Lung tissue was dissolved in tetramethylammonium hydroxide and the diesel soot separated by centrifugation. The soot was suspended in water by sonication and the light absorption of samples was compared to standard suspensions of diesel soot. Recovery from lungs spiked with 50-1000 micrograms of soot was 89 +/- 5%. Rats exposed over a period of 18 weeks to diluted diesel exhaust at average net diesel particles concentrations of 150, 940 and 4100 micrograms/m3 had lung burdens of 35, 220 and 1890 micrograms/g lung, respectively, one day after the last exposure. The long-term clearance rates of soot had estimated half-times of 87 +/- 28, 99 +/- 4 days, for the low and medium exposure groups, respectively. The clearance half-time for the high level exposure group of 165 +/- 8 days was significantly longer (P less than 0.0001) than those of the other two groups.


A selective intramolecular transacylation of taxoids accompanying with the oxetane ring opening.
A selective intramolecular transacylation from C-4 to C-5 of taxoids, which occurred simultaneously with the oxetane D-ring opening and was promoted by TiCl4, was presented. The optimal condition was found to be treatment of substrates in double dose of dichloromethane (per mg of substrate dissolved in 2 mL DCM) with 1 eq of TiCl4 at 25°C for 10 min.


Expression of a two-pore domain K+ channel (TASK-1) in developing avian and mouse ventricular conduction systems.
In this study, we report the identification and amino acid sequence of a novel two-pore domain potassium channel (TASK-1) in chicken. This protein, cTASK-1, is highly similar to mouse and human TASK-1 particularly within the pore regions. We describe the expression profile of both chicken and mouse TASK-1 in the embryonic heart as the ventricular conduction system develops. The developmental distribution of TASK-1 is similar in chicken and mouse. Initially, TASK-1 is expressed throughout the myocardium of the early heart tube. However, as cardiogenesis proceeds, ventricular expression becomes restricted to the trabeculated myocardium and eventually the bundle of His, bundle branches, and Purkinje fibers of the mature conduction system. This finding suggests that components of the ventricular conduction system differentiate from TASK-1-positive myocytes of the early heart tube that retain TASK-1 expression as they mature. Our results are consistent with a common mechanism for ventricular conduction system development in avians and mammals, despite differences in the anatomy of the mature conduction systems of these organisms.


Post-enzymatic hydrolysis heat treatment as an essential unit operation for collagen solubilization from poultry by-products.
Enzymatic protein hydrolysis (EPH) is an invaluable process to increase the value of food processing by-products. In the current work the aim was to study the role of standard thermal inactivation in collagen solubilization during EPH of poultry by-products. Hundred and eighty hydrolysates were produced using two proteases (stem Bromelain and Endocut-02) and two collagen-rich poultry by-products (turkey tendons and carcasses). Thermal inactivation was performed with and without the sediment to study the effect of heat on collagen solubilization. A large difference in molecular weight distribution profiles was observed when comparing hydrolysate time series of the two proteases. In addition, it was shown that 15 min heat treatment, conventionally used for inactivating proteases, is essential in solubilizing collagen fragments, which significantly contributes to increasing the protein yield of the entire process. The study thus demonstrated the possibility of producing tailored products of different quality by exploiting standard heat inactivation in EPH.


The value of endoscopic ultrasonography in preoperative evaluation of rectal cancer.
In rectal cancer, preoperative evaluation of the depth of cancer invasion and the presence of pararectal lymph node metastasis is essential to determine appropriate operative procedures, especially in autonomic nerve preserving operations. For this evaluation, endoscopic ultrasonography (EUS) was performed prospectively in the following cases. During the past 5 years, 70 patients with rectal cancer underwent EUS examination by using 7.5MHz and 12MHz-EUS sonoprobe systems. The depth of cancer invasion was accurately predicted by EUS in 76% of cases (53/70). Seventeen cases were incorrectly estimated, 12 of those underestimated, and 5 overestimated. The evaluation of pararectal lymph node metastasis was accurate in 44 patients (69%). The sensitivity rate was 36% and specificity was 90%. EUS is a very useful technique for determining therapeutic procedures for rectal cancer, especially in deciding whether or not sphincter preserving and/or autonomic nerve preserving operations should be undertaken.