Vowel Production in Prelingually Deafened Mandarin-Speaking Children With Cochlear Implants.
Purpose The purpose of this study was to characterize the acoustic profile and to evaluate the intelligibility of vowel productions in prelingually deafened, Mandarin-speaking children with cochlear implants (CIs). Method Twenty-five children with CIs and 20 age-matched children with normal hearing (NH) were recorded producing a list of Mandarin disyllabic and trisyllabic words containing 20 Mandarin vowels [a, i, u, y, ɤ, ɿ, ʅ, ai, ei, ia, ie, ye, ua, uo, au, ou, iau, iou, uai, uei] located in the first consonant-vowel syllable. The children with CIs were all prelingually deafened and received unilateral implantation before 7 years of age with an average length of CI use of 4.54 years. In the acoustic analysis, the first two formants (F1 and F2) were extracted at seven equidistant time locations for the tested vowels. The durational and spectral features were compared between the CI and NH groups. In the vowel intelligibility task, the extracted vowel portions in both NH and CI children were presented to six Mandarin-speaking, NH adult listeners for identification. Results The acoustic analysis revealed that the children with CIs deviated from the NH controls in the acoustic features for both single vowels and compound vowels. The acoustic deviations were reflected in longer duration, more scattered vowel categories, smaller vowel space area, and distinct formant trajectories in the children with CIs in comparison to NH controls. The vowel intelligibility results showed that the recognition accuracy of the vowels produced by the children with CIs was significantly lower than that of the NH children. The confusion pattern of vowel recognition in the children with CIs generally followed that in the NH children. Conclusion Our data suggested that the prelingually deafened children with CIs, with a relatively long duration of CI experience, still showed measurable acoustic deviations and lower intelligibility in vowel productions in comparison to the NH children.


Broadly Reactive Real-Time RT-PCR Assay for the Detection of Hepatitis E Virus and Simultaneous Genotyping by Single Nucleotide Polymorphism Analysis.
Hepatitis E virus (HEV) infection is a global public health concern. Although HEV infection is usually asymptomatic and self-limiting, extrahepatic manifestations and chronic infections in immunocompromised patients have been described. HEV strains infecting humans have been classified into four main genotypes. In this study we have developed and validated a novel sensitive real-time RT-PCR assay for the detection of all four HEV genotypes. Simultaneous discrimination of genotypes 1, 2, and 4 from genotype 3 by single nucleotide polymorphism (SNP) analysis was possible. In all, 201 serum samples from cases and carriers previously tested for HEV by nested RT-PCR were analyzed. Twenty-seven HEV-positive samples could not be typed by the nested RT-PCR and nucleotide sequencing, but were newly typed by SNP analysis. As polymorphisms were present at the primer or probe binding site, we adopted a degenerate primer and mixed probes. When a mixed probe was added, the fluorescence intensity increased, facilitating genotype determination. IMPORTANCE The distribution of HEV-3 and HEV-4 has been changing. HEV-4, which had been predominantly found in Asia, is now being detected in other parts of the world, and there are now reports of chronic infections. Additionally, neurological disorders have frequently been reported in patients with acute or chronic HEV infections. HEV-4 has also been shown to lead to a higher severity in terms of acute hepatitis than does HEV-3. Early typing can provide useful information regarding the route of infection and for tailoring treatment to the expected course of the disease. The present method afforded a good detection rate even when polymorphisms were present within the target region for viral gene detection. We believe that this method can be applied to the analysis of mutation-prone viral genes in the future.


The diagnostic efficacy of fine-needle aspiration using cytology and culture in tuberculous lymphadenitis.
To retrospectively assess the diagnostic efficacy of fine-needle aspiration (FNA) using cytological and microbiological examinations in tuberculous lymphadenitis. Patients with tuberculous lymphadenitis treated at St Mary's Hospital, London, between January 2001 and June 2007 were identified. The cytological and microbiological reports of 97 patients were found. The criteria for a definite diagnosis of tuberculous lymphadenitis were based on a compatible clinical history, tuberculin positivity and either an indicative cytological result or positive culture. In 77 of the 97 (79%) cases, FNA cytology showed evidence of a tuberculous process. In 65 cases, Mycobacterium tuberculosis was cultured from the aspirates, and 54 of these 65 cases showed corresponding cytological evidence of a tuberculous process; 23 cases were diagnosed by cytology but not microbiology, while 11 cases were diagnosed by microbiology but not cytology. Cytological and microbiological results appeared to correlate well, but each also gives an exclusive diagnosis. When combining both modalities, the diagnostic efficacy of FNA rises to 91%. A definitive microbiological diagnosis was achieved in 67% of cases and provided information on drug susceptibility. We conclude that samples should be provided for both cytological and microbiological examination when using FNA to diagnose possible tuberculous lymphadenitis.


The association of vacA genotype and Helicobacter pylori-related disease in Latin American and African populations.
In the populations of Western countries, particular genotypes of the vacuolating cytotoxin gene, vacA (vacA s, signal region variants; vacA m, middle region variants) of Helicobacter pylori are believed to be risk factors for the development of peptic ulcers and gastric cancer. However, it was unclear whether these vacA gene variants are associated with the development of gastrointestinal diseases in developing nations. The relationship between vacA genotypes and H. pylori-related disease development in Latin American and African populations was investigated using meta-analysis of 2612 patients from Latin America (2285 strains) and 520 patients from Africa (434 strains). The frequencies of vacA s and m genotypes differed between strains from Latin America (77.2% for s1 and 68.1% for m1) and Africa (83.9% for s1 and 56.7% for m1). Latin American strains with s1 and m1 genotypes increased the risk of gastric cancer (OR 4.17, 95% CI 2.49-6.98 for s1, and 3.59, 2.27-5.68 for m1) and peptic ulcers (e.g. 1.73, 1.37-2.20 for s1). African strains with the s1 or m1 genotypes also increased the risk of peptic ulcers (8.69, 1.16-64.75 for s1) and gastric cancer (10.18, 2.36-43.84 for m1). The cagA-positive genotype frequently coincided with s1 and m1 genotypes in both populations. Overall, the vacA s and m genotypes were related to gastric cancer and peptic ulcer development and might be useful markers of risk factors for gastrointestinal disease, especially in Latin America. Further studies will be required to evaluate the effects of vacA genotypes in African populations because of the small sample number currently available.


Recurrent unilateral lung hyperinflation as a manifestation of "auto-PEEP".
Recurrent right lung hyperinflation developed in a 68-year-old man with chronic airflow obstruction. His past history was significant for tuberculosis in the left lung requiring a left upper lobe resection and residual bronchiectasis in the remaining lung. Recognition of the unilateral lung hyperinflation as being a manifestation of unintentional positive end-expiratory pressure (auto-PEEP) resulted in appropriate measures to reverse the process and prevent further complications such as barotrauma. Patients with chronic airflow obstruction and an inflammatory or fibrotic disease process primarily involving one lung are at risk for the development of this atypical presentation of auto-PEEP.


Retroviral vector-mediated transfer of the galactocerebrosidase (GALC) cDNA leads to overexpression and transfer of GALC activity to neighboring cells.
Galactocerebrosidase (GALC) is responsible for the lysosomal catabolism of certain galactolipids, including galactosylceramide and psychosine. Patients with GALC deficiency have an autosomal recessive disorder known as globoid cell leukodystrophy (GLD) or Krabbe disease. Storage of undegraded glycolipids results in defective myelin and the characteristic globoid cells observed on pathological examination of the central and peripheral nervous systems. Most patients have the infantile form of GLD, although older individuals are also diagnosed. Recently the human, mouse, and canine GALC genes were cloned, and mutations causing GLD have been identified. We now describe the construction of a vector containing human GALC cDNA (MFG-GALC), and the transduction of cultured skin fibroblasts from molecularly characterized Krabbe disease patients, as well as rat brain astrocytes and human CD34(+) hematopoietic cells, using retrovirus produced by the psi-CRIP amphotropic packaging cell line. The transduced fibroblasts showed extremely high GALC activity (up to 20,000 times pretreatment levels, about 100 times normal). GALC was secreted into the media and was taken up by untransduced fibroblasts from the same or a different patient. Mannose-6-phosphate receptor-mediated uptake was only partially responsible for the efficient transfer of GALC to neighboring cells. Additional studies confirmed the presence of normal GALC cDNA and mRNA in the transduced cells. The GALC produced by the transduced cells and donated to neighboring untransduced cells was localized to lysosomes as demonstrated by the normal metabolism of [14C]stearic acid-labeled galactosylceramide produced from endocytosed [14C]sulfatide.


Rapid, transient potentiation of dendritic spines in context-induced relapse to cocaine seeking.
Addiction to cocaine produces long-lasting, stable changes in brain synaptic physiology that might contribute to the vulnerability to relapse. In humans, exposure to environmental contexts previously paired with drug use precipitates relapse, but the neurobiological mechanisms mediating this process are unknown. Initiation of cocaine relapse via re-exposure to a drug-associated context elicited reinstatement of cocaine seeking as well as rapid, transient synaptic plasticity in the nucleus accumbens core (NAcore), measured as an increase in dendritic spine diameter. These results show that rapid context-evoked synaptic potentiation in the NAcore may underpin relapse to cocaine use.


Flexural Behavior and Fracture Mechanisms of Short Carbon Fiber Reinforced Polyether-Ether-Ketone Composites at Various Ambient Temperatures.
In this study, the flexural behavior and fracture mechanisms of short carbon fiber reinforced polyether-ether-ketone (SCFR/PEEK) composites at various ambient temperatures were investigated. First, the crystallinity and glass transition temperature (Tg) of PEEK and SCFR/PEEK were analyzed by differential scanning calorimetry analysis and dynamic mechanical analysis tests, respectively. The addition of SCFs increases the Tg but does not change the crystallinity of the PEEK matrix. Then, the three-point flexural tests of PEEK and SCFR/PEEK were performed over the temperature range of 20 to 235 °C, and the temperature-dependencies of the flexural properties of PEEK and SCFR/PEEK were discussed in detail. Finally, the microstructure of SCFR/PEEK was observed using a digital microscope and scanning electron microscope. The results show that the tension crack occurs first, and the crack extends upward leading to the shear crack and compression crack at room temperature. The fracture of SCFR/PEEK is mainly due to the extraction and rupture of SCFs. At high temperatures (above Tg), the tension crack and compression crack both occur, and the strong ductility of the matrix prevents the generation of shear crack. The fracture of SCFR/PEEK is mainly due to the rotation and extraction of SCFs, while the SCFs rupture plays a minor role.


Recruitment of ORC or CDC6 to DNA is sufficient to create an artificial origin of replication in mammalian cells.
Origins of replication are expected to recruit initiation proteins like origin recognition complex (ORC) and Cdc6 in eukaryotes and provide a platform for unwinding DNA. Here we test whether localization of initiation proteins onto DNA is sufficient for origin function. Different components of the ORC complex and Cdc6 stimulated prereplicative complex (pre-RC) formation and replication initiation when fused to the GAL4 DNA-binding domain and recruited to plasmid DNA containing a tandem array of GAL4-binding sites. Replication occurred once per cell cycle and was inhibited by Geminin, indicating that the plasmid was properly licensed during the cell cycle. The GAL4 fusion protein recruits other polypeptides of the ORC-Cdc6 complex, and nascent strand abundance was highest near the GAL4-binding sites. Therefore, the artificial origin recapitulates many of the regulatory features of physiological origins and is valuable for studies on replication initiation in mammalian cells. We demonstrated the utility of this system by showing the functional importance of the ATPase domains of human Cdc6 and Orc1 and the dispensability of the N-terminal segments of Orc1 and Orc2 in this assay. Artificial recruitment of a eukaryotic cellular replication initiation factor to a DNA sequence can create a functional origin of replication, providing a robust genetic assay for these factors and a novel approach to generating episomal vectors for gene therapy.


Fish-borne nematodiases in South America: neglected emerging diseases.
Fish-borne zoonotic nematodes may infect humans when fish or squid are ingested raw or inadequately cooked. Human infections may have serious consequences, including the unexpected deaths of infected people. This kind of disease is poorly known in general, and the characteristics of such infections in South American countries as a whole have never been assessed. In this paper the present status of fish-borne nematodiases in humans in South American countries is characterized. Potentially zoonotic nematode species are very common in both freshwater and marine fish in South America. Reports of human infections have only been found in some countries, and their incidence (especially with anisakids and Gnathostoma spp.) varies from country to country. Apparently they are more abundant in countries with strong traditions of eating raw fish, and are more frequent on the western coast of South America. So far fish-borne nematodes have been reported in Argentina, Brazil, Chile, Colombia, Ecuador and Peru. In recent years, cases of human infection have appeared in probably underestimated numbers. People need to be clearly informed about risky feeding habits, and physicians need to learn more about zoonotic diseases.


Cleidocranial dysplasia: diagnostic criteria and combined treatment.
Cleidocranial dysplasia (CCD) is an uncommon, generalized skeletal disorder characterized by delayed ossification of the skull, aplastic or hypoplastic clavicles, and serious, complex dental abnormalities. There are many difficulties in the early diagnosis of CCD because a majority of the craniofacial abnormalities becomes obvious only during adolescence. In the present case, a hypoplastic midface, a relative prognathia of the mandible, and close approximation of the shoulders in the anterior plane were the conspicuous extraoral findings. Prolonged exfoliation of the primary dentition, unerupted supernumerary teeth, and the irregularly and partially erupted secondary dentition produced occlusional anomalies. The presence of the second permanent molars together with the primary dentition and wide spacing in the lower incisor area were typical dental signs. Gradual extraction of the supernumerary teeth and over-retained primary teeth was the first step of oral surgery. This was followed by a surgical exposure of the unerupted teeth by thinning of the cortical bone. Orthodontic treatment was aimed at parallel growth of the jaws. Removable appliances were used to expand the narrow maxillary and mandibular arches, and a Delaire mask compensated for the lack of sagittal growth of the upper jaw. Temporary functional rehabilitation was solved by partial denture. When the jaws have been fully developed, implant insertions and bridges are the therapeutic measures. The reported case and the literature data support the importance of the early diagnosis and interdisciplinary treatment of CCD.


Alginate microencapsulation of an attenuated O-antigen mutant of Francisella tularensis LVS as a model for a vaccine delivery vehicle.
Francisella tularensis is the etiologic agent of tularemia and a Tier I Select Agent. Subspecies tularensis (Type A) is the most virulent of the four subspecies and inhalation of as few as 10 cells can cause severe disease in humans. Due to its niche as a facultative intracellular pathogen, a successful tularemia vaccine must induce a robust cellular immune response, which is best achieved by a live, attenuated strain. F. tularensis strains lacking lipopolysaccharide (LPS) O-antigen are highly attenuated, but do not persist in the host long enough to induce protective immunity. Increasing the persistence of an O-antigen mutant may help stimulate protective immunity. Alginate encapsulation is frequently used with probiotics to increase persistence of bacteria within the gastrointestinal system, and was used to encapsulate the highly attenuated LVS O-antigen mutant WbtIG191V. Encapsulation with alginate followed by a poly-L-lysine/alginate coating increased survival of WbtIG191V in complement-active serum. In addition, BALB/c mice immunized intraperitoneally with encapsulated WbtIG191V combined with purified LPS survived longer than mock-immunized mice following intranasal challenge. Alginate encapsulation of the bacteria also increased antibody titers compared to non-encapsulated bacteria. These data suggest that alginate encapsulation provides a slow-release vehicle for bacterial deposits, as evidenced by the increased antibody titer and increased persistence in serum compared to freely suspended cells. Survival of mice against high-dose intranasal challenge with the LVS wildtype was similar between mice immunized within alginate capsules or with LVS, possibly due to the low number of animals used, but bacterial loads in the liver and spleen were the lowest in mice immunized with WbtIG191V and LPS in beads. However, an analysis of the immune response of surviving mice indicated that those vaccinated with the alginate vehicle upregulated cell-mediated immune pathways to a lesser extent than LVS-vaccinated mice. In summary, this vehicle, as formulated, may be more effective for pathogens that require predominately antibody-mediated immunity.


Diatoms on the carapace of common snapping turtles: Luticola spp. dominate despite spatial variation in assemblages.
Filamentous algae are often visible on the carapaces of freshwater turtles and these algae are dominated by a few species with varying geographic distributions. Compared to filamentous algae, little is known about the much more speciose microalgae on turtles. Our objectives were to compare the diatom flora on a single turtle species (the common snapping turtle, Chelydra serpentina) across part of its range to examine spatial patterns and determine whether specific diatom taxa were consistently associated with turtles (as occurs in the filamentous alga Basicladia spp.). Using preserved turtle specimens from museums, we systematically sampled diatoms on the carapaces of 25 snapping turtles across five states. The diverse diatom assemblages formed two groups-the southern Oklahoma group and the northern Illinois/Wisconsin/New York group, with Arkansas not differing from either group. Of the six diatom species found in all five states, four species are widespread, whereas Luticola cf. goeppertiana and L. cf. mutica are undescribed species, known only from turtles in our study. L. cf. goeppertiana comprised 83% of the diatom abundance on Oklahoma turtles and was relatively more abundant on southern turtles (Oklahoma and Arkansas) than on northern turtles (where mean abundance/state was > 10%). L. cf. mutica was the most abundant species (40%) on New York turtles. Some Luticola species are apparently turtle associates and results support a pattern of spatial variation in Luticola species, similar to that in Basicladia. Using museum specimens is an efficient and effective method to study the distribution of micro-epibionts.


Alliance predicting progress in couple therapy.
The therapeutic alliance has gained status as a common factor in psychotherapy due to its robust predictive relationship with outcome. The current challenge in our field is to gain a more nuanced understanding of alliance's impact on the progress of treatment over the course of therapy. In the current study, alliance was measured on 3 dimensions: (a) the individual's as well as the couple's joint perception of alliance with the therapist ("self/group-therapist"), (b) each partner's perception of the alliance between the spouse and the therapist ("other-therapist"), and (c) the couple's assessment of alliance with each other ("within-system"). Based on self-reported data from 165 adult clients, we analyzed whether scores on these alliance dimensions at the beginning of therapy predicted the frequently measured outcomes on individual symptoms and relationship distress during treatment. We found that 2 of the alliance dimensions, the "self/group-therapist" and the "other-therapist," at the start of treatment predicted the slopes of the outcome measures. These findings add to established research suggesting that early establishment of alliance is an important predictor for progress during treatment. Variations in the results among the 3 alliance dimensions suggest the usefulness of the clinician assessing different aspects of alliance in couple therapy. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Who helps the helper? Differentiation of self as an indicator for resisting vicarious traumatization.
This study comprises a first attempt to explain and predict vicarious traumatization among therapists by means of Bowen's Family Systems Theory (Bowen, 1978), especially with reference to the phenomenon "differentiation of self," a central feature of his theory. A sample of 134 individual and group therapists who work in public and private clinics completed a series of questionnaires that provided data regarding demographic information, differentiation of self, and a belief scale that measures the existence of vicarious trauma. The findings indicate a strong negative correlation between vicarious traumatization and differentiation of self. In addition, participant age and "being in therapy" were both found to correlate with differentiation of self and vicarious traumatization. These findings point to the importance of differentiation of self as a resilience factor protecting against vicarious trauma, and have the potential to contribute to the development of tools for efficiently and accurately assessing predisposition toward vicarious traumatization among therapists. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


A dislocation of the inner head in bipolar prosthesis with a self-centering system: a case report.
We present a case of inner head dislocation 11 years after the replacement of a bipolar prosthesis with a self-centering system. An 84-year-old woman with osteoarthritis of the left hip underwent a replacement of the Bateman UPF-II bipolar prosthesis in 1987. She fell off a chair on April 19 1998, and felt a sudden sharp pain in the left hip. Roentgenograms revealed that the inner head was dislocated from the outer head. Moreover, on June 19, when she stood up from the floor, the dislocation recurred. On July 23, a revision surgery was carried out. When the outer head was removed from the acetabulum, the bearing insert was markedly worn by the impingement of the femoral stem neck. Because there was no evidence of loosening of the femoral stem, a cemented replacement of the acetabular component was performed. At a 2-year follow-up, she had mild hip pain, but had returned fully to daily living. Our review of current published studies reveals that most inner head dislocations occurred in osteoarthritic patients. Thus, the occurrence of dislocations may be more dependent on patient selection than on failure of the bipolar prosthesis itself.


Comparative study of matrix metalloproteinase expression between African American and Caucasian Women.
To date there are 26 human matrix metalloproteinases (MMPs) which are classified according to their substrate specificity and structural similarities. The four major subgroups of MMPs are gelatinases, interstitial collagenases, stromelysins, and membrane-type matrix metalloproteinases (MT-MMPs). This study investigates the expression of 26 MMPs, which have been shown to play a role in cancer metastasis. Breast tissues and cell lines derived from African American patients and Caucasian patients were assayed to demonstrate alterations in the transcription of genes primarily responsible for degrading the extracellular matrix (ECM). The expression levels of the extracellular matrix and adhesion molecules were analyzed using the gene array technology. Steady state levels of mRNAs were validated by RT-PCR analysis. Total RNA was isolated from tissue and cell lines and used in the RT-PCR assays. From this data, differential expression of MMPs between 6 breast cancer cell lines and 2 non-cancer breast cell lines was demonstrated. We have performed an in vitro comparison of MMP expression and established differences in 12 MMPs (3, 7, 8, 9, 11-15, 23B, 26, and 28) expression between African American and Caucasian breast cell lines. Thus, evidence indicates that altered expression of MMPs may play a role in the aggressive phenotype seen in African American women.


A nationwide analysis of pancreatic cancer trial enrollment reveals disparities and participation problems.
Our research group recently surveyed the clinical trial landscape in pancreatic adenocarcinoma and identified 430 active trials. These represent an opportunity to expand treatment options for patients with pancreatic adenocarcinoma. Our primary objective was to detail clinical trial participation among patients with pancreatic adenocarcinoma. Our secondary objective was to evaluate survival. We queried the National Cancer Database (2004-2016) for patients with pancreatic adenocarcinoma. Patients were stratified by trial participation: clinical trial or non-trial. Multivariable logistic regression was used to identify variables associated with trial participation. The Kaplan-Meier method and multivariable Cox hazards regression were used to analyze survival. In total, 261,483 patients were included: 1,110 (0.4%) were enrolled in a clinical trial. A total of 57 Black patients participated in a clinical trial (0.19% of Black patients). This was lower compared to White patients (n = 955, 0.49% of White patients, P < .001). After adjusting for demographic and clinical factors, Black patients were less likely to be enrolled in a clinical trial (odds ratio = 0.387, P < .001). Patients treated at nonacademic medical centers were less likely to be in a clinical trial. Trial participation was associated with an increased median survival relative to non-trial patients (stage IV: 9.0 vs 3.8 months, P < .001), and this association remained on multivariable regression (hazard ratio = 0.779, P < .001). Fewer than 1% of patients with pancreatic adenocarcinoma participated in a clinical trial. There are racial and sociodemographic disparities in clinical trial enrollment. An association was observed between clinical trial participants and prolonged survival.


Mitochondrial DNA as a Possible Ligand for TLR9 in Irinotecan-induced Small Intestinal Mucositis.
Cancer chemotherapy and radiotherapy may result in mucositis characterized by stem cell damage and inflammation in the gastrointestinal tract. The molecular mechanisms underlying this pathology remain unknown. Based on the assumption that mitochondrial CPG-DNA (mtDNA) released and sensed by TLR9 could underlie mucositis pathology, we analyzed the mtDNA levels in sera as well as inflammatory and disease parameters in the small intestine from wild-type (WT) and TLR9-deficient mice (TLR9-/-) in an experimental model of intestinal mucositis induced by irinotecan. Additionally, we verified the ability of WT and TLR9-/- macrophages to respond to CpG-DNA in vitro. WT mice injected with irinotecan presented a progressive increase in mtDNA in the serum along with increased hematocrit, shortening of small intestine length, reduction of intestinal villus:crypt ratio and increased influx of neutrophils, which were followed by higher expression of Nlrp3 and Casp1 mRNA and increased IL-1β levels in the ileum when compared to vehicle-injected mice. TLR9-deficient mice were protected in all these parameters when compared to WT mice. Furthermore, TLR9 was required for the production of IL-1β and NO after macrophage stimulation with CpG-DNA. Overall, our findings show that the amount of circulating free CpG-DNA is increased upon chemotherapy and that TLR9 activation is important for NLRP3 inflammasome transcription and further IL-1β release, playing a central role in the development of irinotecan-induced intestinal mucositis. We suggest that TLR9 antagonism may be a new therapeutic strategy for limiting irinotecan-induced intestinal inflammation.


Behavioral drivers and observation of face covering use during the COVID-19 pandemic among outpatients and visitors at a tertiary hospital in Thailand.
Use of face covering may help prevent COVID-19 transmission. However, there is a lack of data on behavioral drivers of face covering use and compliance to mandatory face covering policy at health facilities. This study aimed to describe behavioral drivers and observed face covering use among outpatients and visitors at a tertiary hospital in Southern Thailand during the COVID-19 pandemic. We conducted a hospital-based, cross-sectional study in June 2020. We developed, pilot-tested and finalized an interview questionnaire in Thai. We also developed a structured observation questionnaire. Two trained enumerators recruited outpatients and visitors at the hospital's internal medicine outpatient department (OPD), surgery OPD, and the pharmacy using the convenience sampling. Another enumerator conducted structured observation of face covering use among outpatients and visitors when interviews were not taking place. We analyzed the data using the descriptive statistics. A total of 206 persons that our interview enumerators approached agreed to participate (n = 206; response rate = 62.4%). Nearly all participants stated that the use of face covering was beneficial in preventing COVID-19 infection from others and preventing others from being infected (94.0% and 98.0%, respectively). Common barriers included inconvenience in breathing and speaking (19.7%) and pain at the ears (9.6%). Structured observation of 408 outpatients and visitors showed that nearly everyone (>99%) had a face covering on their person, most of whom (94.6%) covered both their nose and mouth. We found near-universal perceived benefits and compliance, but variations in perceived barriers, cues, and social norms for the use of face coverings. The findings of this study can inform future intervention programs on face covering use promotion.


Extracorporeal cardiopulmonary resuscitation: is it futile?
Extracorporeal cardiopulmonary resuscitation (ECPR) is a treatment modality used to restore end-organ perfusion in the setting of refractory cardiac arrest in patients receiving cardiopulmonary resuscitation (CPR). Despite advances in medicine, survival from cardiac arrest remains low with conventional CPR. The body of literature relating to ECPR is limited to retrospective studies and case series, with data that are inconsistent. Routine use of ECPR is not currently endorsed by the American Heart Association. In several single-center retrospective studies, ECPR was associated with a higher level of return of spontaneous circulation and survival to hospital discharge, when compared with conventional CPR. However, data from larger population-based registry studies have not reproduced these findings. Implementation of ECPR is a complex endeavor that requires specialized, multidisciplinary expertise to be successful. ECPR may be considered as an adjunct to CPR in cases of refractory cardiac arrest. The success of ECPR relies on specialized expertise, thoughtful patient selection, and timely initiation.


Fiber-Optic System for Monitoring Pressure Changes on Mine Support Elements.
The paper presents the developed fiber-optic sensors for monitoring pressure measurement on the elements of mine supports. The sudden destruction of the support leads to the collapse of the mine workings and poses a serious threat to the life and safety of underground workers. A fiber-optic system for monitoring changes in pressures on the elements of mine supports will increase the share of mining automation and reduce the share of manual labor, as well as eliminate measurement errors associated with the human factor. Systematic monitoring of the state of the working elements of the support will allow timely tracking of their deformations caused by an increase in rock pressure on them. Implementation of the system at mining enterprises will expand the use of digital technologies in mining. Timely warning of a mine collapse threat will significantly increase the level of safe mining operations, as well as reduce the cost of supporting mine workings, since elimination of the consequences of destruction is associated with significant material costs. This work presents a developed laboratory testbench that simulates a mine working and elements of an arch support on which are installed the fiber-optic sensors connected to an automated measuring system. The developed hardware and software complex provides the processing of a light spot falling on the surface of a television matrix that is installed at the exit from the optical fiber. The results of visual processing are converted into numerical values, which are used to make a decision about the state of the considered object. In addition to automatic monitoring of the structural integrity condition of the considered object, the system is equipped with a function of a visual display for monitoring results, which makes it possible to track sharp fluctuations and bursts of pressure parameters, based on which the prediction of pre-emergency and emergency situations is performed.


Crossmodal binding rivalry: A "race" for integration between unequal sensory inputs.
Exposure to multiple but unequal (in number) sensory inputs often leads to illusory percepts, which may be the product of a conflict between those inputs. To test this conflict, we utilized the classic sound induced visual fission and fusion illusions under various temporal configurations and timing presentations. This conflict between unequal numbers of sensory inputs (i.e., crossmodal binding rivalry) depends on the binding of the first audiovisual pair and its temporal proximity to the upcoming unisensory stimulus. We, therefore, expected that tight coupling of the first audiovisual pair would lead to higher rivalry with the upcoming unisensory stimulus and, thus, weaker illusory percepts. Loose coupling, on the other hand, would lead to lower rivalry and higher illusory percepts. Our data showed the emergence of two different participant groups, those with low discrimination performance and strong illusion reports (particularly for fusion) and those with the exact opposite pattern, thus extending previous findings on the effect of visual acuity in the strength of the illusion. Most importantly, our data revealed differential illusory strength across different temporal configurations for the fission illusion, while for the fusion illusion these effects were only noted for the largest stimulus onset asynchronies tested. These findings support that the optimal integration theory for the double flash illusion should be expanded so as to also take into account the multisensory temporal interactions of the stimuli presented (i.e., temporal sequence and configuration).


c-myc activation renders proliferation of Epstein-Barr virus (EBV)-transformed cells independent of EBV nuclear antigen 2 and latent membrane protein 1.
Two genetic events contribute to the development of endemic Burkitt lymphoma (BL) infection of B lymphocytes with Epstein-Barr virus (EBV) and the activation of the protooncogene c-myc through chromosomal translocation. The viral genes EBV nuclear antigen 2 (EBNA2) and latent membrane protein 1 (LMP1) are essential for transformation of primary human B cells by EBV in vitro; however, these genes are not expressed in BL cells in vivo. To address the question whether c-myc activation might abrogate the requirement of the EBNA2 and LMP1 function, we have introduced an activated c-myc gene into an EBV-transformed cell line in which EBNA2 was rendered estrogen-dependent through fusion with the hormone binding domain of the estrogen receptor. The c-myc gene was placed under the control of regulatory elements of the immunoglobulin kappa locus composed a matrix attachment region, the intron enhancer, and the 3' enhancer. We show here that transfection of a c-myc expression plasmid followed by selection for high MYC expression is capable of inducing continuous proliferation of these cells in the absence of functional EBNA2 and LMP1. c-myc-induced hormone-independent proliferation was associated with a dramatic change in the growth behavior as well as cell surface marker expression of these cells. The typical lymphoblastoid morphology and phenotype of EBV-transformed cells completely changed into that of BL cells in vivo. We conclude that the phenotype of BL cells reflects the expression pattern of viral and cellular genes rather than its germinal center origin.


What the American Journal of Critical Care Junior Peer Reviewers Were Reading During Year 2 of the Program.
The American Journal of Critical Care's Junior Peer Reviewer program aims to mentor novice reviewers in the peer review process. To grow their critical appraisal skills, the participants take part in discussion sessions in which they review articles published in other journals. Here we summarize the articles reviewed during the second year of the program, which again focused on the care of critically ill patients with COVID-19. This article aims to share these reviews and the reviewers' thoughts regarding the relevance, design, and applicability of the findings from the selected studies. High rates of delirium associated with COVID-19 may be impacted by optimizing sedation strategies and allowing safe family visitation. Current methodology in crisis standards of care may result in inequity and further research is needed. The use of extracorporeal carbon dioxide removal to facilitate super low tidal volume ventilation does not improve 90-day mortality outcomes. Continued research to better understand the natural history of COVID-19 and interventions useful for improving outcomes is imperative.


Assessment of Alkylated and Unsubstituted Polycyclic Aromatic Hydrocarbons in Air in Urban and Semi-Urban Areas in Toronto, Canada.
22 alkylated polycyclic aromatic hydrocarbons (alk-PAHs) were characterized in ambient air individually for the first time in urban and semi-urban locations in Toronto, Canada. Five unsubstituted PAHs were included for comparison. Results from the measurements were used to estimate benzo[a]pyrene equivalent toxicity (BaPeq) of individual compounds in order to investigate the significance of a single compound in contributing to the overall toxic equivalency (TEQ) of air mixtures. To determine which compounds merit further investigation, BaPeq values of individual compounds were compared to the measured BaP toxicity. Our results showed that both unsubstituted and alkylated PAHs were more abundant in the urban area (38 and 30%, respectively). Benzo[a]pyrene levels at the urban location exceeded Ontario's 24 h guideline (40% of the events), and on average, it was 5 times higher than that at the semi-urban area. Gas-phase two- and three-ring compounds contributed up to 39% (urban) and 76% (semi-urban) of the TEQ of all compounds analyzed. Some alk-PAHs such as 7,12-dimethylbenzo[a]anthracene had a huge impact on the toxicity of urban air, and its BaPeq was on average 8 times higher than that of BaP. We emphasize that the toxic impact of alkylated and gaseous PAHs, which is not routinely included in many air monitoring programs, is significant and should not be neglected.


A brain-specific G protein gamma subunit.
Two different cDNAs for G protein gamma subunits have been isolated from mouse brain. One encodes a novel gamma subunit, gamma 4, the expression of which is detected only in brain. A fragment of this cDNA had been isolated previously. The other cDNA encodes gamma 3, a subunit type previously isolated from bovine brain. The primary structure of the gamma 3 subunit is conserved completely across species indicating that the diversity in the structure of the gamma subunits is of functional consequence. Moreover, gamma 2, gamma 3 and gamma 4, which are predominantly expressed in brain, are more homologous to each other than other gamma subunits, indicating that the G protein gamma subunits belong to distinct subfamilies similar to the alpha subunits.


Early injection of high-dose recombinant factor VIIa decreases blood loss and prolongs time from injury to death in experimental liver injury.
Recombinant factor VIIa (rFVIIa) is used for treatment of bleeding episodes in hemophilia patients who develop inhibitors to factors VIII and IX. We tested the hypothesis that administration of rFVIIa early after injury would decrease bleeding and prolong the time from injury to death after experimental hepatic trauma. Anesthetized swine were cannulated for blood sampling and hemodynamic monitoring. Avulsion of the left median lobe of the liver induced uncontrolled hemorrhage. After a 10% reduction in mean arterial pressure, animals (n = 8 per group) were blindly randomized to receive intravenous rFVIIa 180 microg/kg, rFVIIa 720 microg/kg, or placebo. Pathologic examination of brain, lung, kidney, heart, and small bowel was performed to assess intravascular thrombosis. RESULTS Mortality during the first hour was 50% (four of eight) in controls versus 0% with rFVIIa 720 microg/kg (p = 0.02, chi2). Blood loss was decreased in the rFVIIa 720 microg/kg group versus the placebo group (13.2 +/- 5.5 mL/kg vs. 21.9 +/- 7.7 mL/kg;p = 0.0223). Time from injury to death was significantly prolonged in the rFVIIa 720 microg/kg group compared with placebo (116 minutes vs. 8.5 +/- 3.5 minutes; p= 0.02). No macro- or microthrombi in vital organs were identified on pathologic examination. Intravenous administration of high-dose rFVIIa early after induction of hemorrhage decreased bleeding and prolonged survival. No evidence of thrombosis in vital organs was observed.


Isolation and structural determination of flavan-3-ol derivatives from the Polypodium vulgare L. rhizomes water extract.
Polypodium vulgare L. (Polypodiaceae) is a fern used in traditional Polish medicine as an expectorant to treat cough and pertussis. Additionally, it was used as a diuretic in renal diseases, especially in chronic nephritis and pyelonephritis. In our study, a water extract was prepared from the rhizome of common polypody and subsequently fractionated on a resin column. As a result, the mixture of flavan-3-ol derivatives was obtained after the column elution with 60% methanol. Further purification by various chromatographic techniques led us to the isolation of (+)-afzelechin (1), a new previously not reported (+)-afzelechin-7-O-α-l-arabinofuranoside (2), and three other monomer flavan-3-ol glycosides: (+)-afzelechin-7-O-β-d-apiofuranoside (3), (+)-catechin-7-O-α-l-arabinofuranoside (4) and (+)-catechin-7-O-β-d-apiofuranoside (5). Structures of the compounds were established by HR-ESI-MS, 1D and 2D NMR spectroscopy. The HSQC and HMBC NMR techniques were used in the structure elucidation of the position of sugar attachment.


Volumetric and Diffusion Abnormalities in Subcortical Nuclei of Older Adults With Cognitive Frailty.
Background: Cognitive frailty (CF) is defined as the simultaneous presence of physical frailty and cognitive impairment among older adults without dementia. Previous studies have revealed that neuropathological changes may contribute to the degeneration of subcortical nuclei in the process of cognitive impairment. However, it is unclear in CF. The aim of this study is to investigate the changes in subcortical nuclei in older adults with CF and their relationship with cognitive decline and physical frailty. Methods: A total of 26 older adults with CF and 26 matched healthy subjects were enrolled. Cognitive function and physical frailty were assessed with the Montreal Cognitive Assessment (MoCA) scale (Fuzhou version) and the Chinese version of the Edmonton Frailty Scale (EFS). Volumetric and diffusion tensor imaging (DTI) parameters of subcortical nuclei were measured with structural and DTI brain magnetic resonance imaging (MRI) and compared between groups. Partial correlation analysis was conducted between subcortical nuclei volumes, MoCA scores, and physical frailty indexes. Results: Significant volume reductions were found in five subcortical nuclei, including the bilateral thalami, left caudate, right pallidum, and accumbens area, in older adults with CF (P < 0.05), and the bilateral thalami was most obvious. Decreased fractional anisotropy and relative anisotropy values were observed only in the left thalamus in the CF group (P < 0.05). No group differences were found in apparent diffusion coefficient (ADC) values. The MoCA scores were positively correlated with the volumes of the bilateral thalami, right pallidum, and accumbens area (P < 0.05). Negative correlations were found between the physical frailty index and the volumes of the bilateral thalami, caudate, pallidum, and right accumbens area (P < 0.05). Conclusion: Microstructural changes occur in the subcortical nuclei of older adults with CF, and these changes are correlated with cognitive decline and physical frailty. Therefore, microstructural atrophy of the subcortical nuclei may be involved in the pathological progression of CF.


Effect of climatic variability on childhood diarrhea and its high risk periods in northwestern parts of Ethiopia.
Increasing climate variability as a result of climate change will be one of the public health challenges to control infectious diseases in the future, particularly in sub-Saharan Africa including Ethiopia. To investigate the effect of climate variability on childhood diarrhea (CDD) and identify high risk periods of diarrheal diseases. The study was conducted in all districts located in three Zones (Awi, West and East Gojjam) of Amhara Region in northwestern parts of Ethiopia. Monthly CDD cases for 24 months (from July 2013 to June 2015) reported to each district health office from the routine surveillance system were used for the study. Temperature, rainfall and humidity data for each district were extracted from satellite precipitation estimates and global atmospheric reanalysis. The space-time permutation scan statistic was used to identify high risk periods of CDD. A negative binomial regression was used to investigate the relationship between cases of CDD and climate variables. Statistical analyses were conducted using SaTScan program and StataSE v. 12. The monthly average incidence rate of CDD was 11.4 per 1000 (95%CI 10.8-12.0) with significant variation between males [12.5 per 1000 (95%CI 11.9 to 13.2)] and females [10.2 per 1000 (95%CI 9.6 to 10.8)]. The space-time permutation scan statistic identified the most likely high risk period of CDD between March and June 2014 located in Huletej Enese district of East Gojjam Zone. Monthly average temperature and monthly average rainfall were positively associated with the rate of CDD, whereas the relative humidity was negatively associated with the rate of CDD. This study found that the most likely high risk period is in the beginning of the dry season. Climatic factors have an association with the occurrence of CDD. Therefore, CDD prevention and control strategy should consider local weather variations to improve programs on CDD.


Interference in the anti-Xa heparin activity assay due to hemolysis and icterus during pediatric extracorporeal life support.
Chromogenic anti-Xa assays for unfractionated heparin monitoring (heparin activity) are susceptible to interference from hemolysis and icterus. The purpose of this study was to better understand the effect of hemolysis and icterus on anti-Xa heparin activity and to predict the magnitude of the error. Increasing levels of hemoglobin and unconjugated bilirubin were added to pooled normal plasma or buffer containing known levels of heparin. Increased plasma hemoglobin or bilirubin produced falsely increased residual factor Xa activity as measured by the absorbance change (OD/min) in the Stago heparin activity assay. This increased absorbance change slope resulted in falsely lower estimates of heparin activity. The falsely lower heparin activity measurement occurred even when heparin was not present, indicating it was not due to heparin neutralization. In a sample containing 0.62 ± 0.06 U/mL heparin and 228 mg/dL hemoglobin, the measured heparin activity was 0.41 ± 0.03 U/mL, underestimating heparin activity by 0.21 ± 0.07 U/mL. Interference occurred if plasma hemoglobin was above 70 mg/dL or bilirubin was above 16 mg/dL, which happened in 16%-26% of samples from pediatric patients on extracorporeal life support (ECLS). In conclusion, hemolysis and icterus were common in ECLS patients, leading to underestimates of unfractionated heparin activity and potentially higher doses of heparin than intended. The magnitude of the heparin activity measurement error could be predicted based on plasma hemoglobin and bilirubin levels until these levels exceeded the technical limits of the assay, ~230 mg/dL hemoglobin and 55 mg/dL bilirubin.


Combined administration of recombinant human megakaryocyte growth and development factor and granulocyte colony-stimulating factor enhances multilineage hematopoietic reconstitution in nonhuman primates after radiation-induced marrow aplasia.
This study compared the therapeutic potential of recombinant, native versus pegylated megakaryocyte growth and development factor (rMGDF and PEG-rMGDF, respectively), as well as that of the combined administration of PEG-rMGDF and r-methionyl human granulocyte colony-stimulating factor (r-metHuG-CSF) on hematopoietic reconstitution after 700 cGy, 60Co gamma, total body irradiation in nonhuman primates. After total body irradiation, animals received either rMGDF, PEG-rMGDF, r-metHuG-CSF, PEG-rMGDF and r-metHuG-CSF or HSA. Cytokines in all MGDF protocols were administered for 21-23 d. Either rMGDF, PEG-rMGDF, or PEG-rMGDF and r-metHuG-CSF administration significantly diminished the thrombocytopenic duration (platelet count (PLT) < 20,000 per microliter)to o.25, 0, 0.5 d, respectively, and the severity of the PLT nadir (28,000, 43,000, and 30,000 per microliter, respectively) as compared with the controls (12.2 d duration, nadir 4,000 per microliter), and elicited an earlier PLT recovery. Neutrophil regeneration was augmented in all cytokine protocols and combined PEG-rMGDF and r-metHuG-CSF further decreased the duration of neutropenia compared with r-metHuG-CSF alone. These data demonstrated that the administration of PEG-rMGDF significantly induced bone marrow regeneration versus rMGDF, and when combined with r-metHuG-CSF significantly enhanced multilineage hematopoietic recovery with no evidence of lineage competition.


Surgical management of large segmental femoral and radial bone defects in a dog: through use of a cylindrical titanium mesh cage and a cancellous bone graft.
In this case report, we describe the use of a cylindrical titanium mesh cage combined with cancellous bone graft to surgically manage large segmental bone defects in a dog. A seven-year-old, neutered male cross-breed dog, with highly comminuted fractures of the right femur and the left radius and ulna, was referred for treatment. Previous open reduction and internal fixation of these fractures had failed. Following implant removal and debridement of each bone, a 71 mm segmental femoral defect and a 27 mm segmental radial defect were present. A commercially available cylindrical titanium mesh cage was filled with ss-tricalcium phosphate crystals mixed with an equal volume of autogenous cancellous bone graft. The mesh cage was aligned with the proximal and distal parts of each bone using an intramedullary pin passing through the cage, and a locking plate was applied to the proximal and distal fracture fragments to produce compression against the titanium cage. The dog had a successful long-term clinical outcome, and radiographic examination at 22 and 63 weeks after surgery showed the formation of remodelling bridging callus that was continuous across the titanium cage in each of the fractures. Due to the relative simplicity of the technique and the favourable outcome in this case, it should be considered an option when managing comminuted fractures with large bone defects.


Action planning and affective states within the auditory peripersonal space in normal hearing and cochlear-implanted listeners.
Fast reaction to approaching stimuli is vital for survival. When sounds enter the auditory peripersonal space (PPS), sounds perceived as being nearer elicit higher motor cortex activation. There is a close relationship between motor preparation and the perceptual components of sounds, particularly of highly arousing sounds. Here we compared the ability to recognize, evaluate, and react to affective stimuli entering the PPS between 20 normal-hearing (NH, 7 women) and 10 cochlear-implanted (CI, 3 women) subjects. The subjects were asked to quickly flex their arm in reaction to positive (P), negative (N), and neutral (Nu) affective sounds ending virtually at five distances from their body. Pre-motor reaction time (pm-RT) was detected via electromyography from the postural muscles to measure action anticipation at the sound-stopping distance; the sounds were also evaluated for their perceived level of valence and arousal. While both groups were able to localize sound distance, only the NH group modulated their pm-RT based on the perceived sound distance. Furthermore, when the sound carried no affective components, the pm-RT to the Nu sounds was shorter compared to the P and the N sounds for both groups. Only the NH group perceived the closer sounds as more arousing than the distant sounds, whereas both groups perceived sound valence similarly. Our findings underline the role of emotional states in action preparation and describe the perceptual components essential for prompt reaction to sounds approaching the peripersonal space.


Systematic Review: Clinical Metabolomics to Forecast Outcomes in Liver Transplantation Surgery.
Liver transplantation is an effective intervention for end-stage liver disease, fulminant hepatic failure, and early hepatocellular carcinoma. Yet, there is marked patient-to-patient variation in liver transplantation outcomes. This calls for novel diagnostics to enable rational deployment of donor livers. Metabolomics is a postgenomic high-throughput systems biology approach to diagnostic innovation in clinical medicine. We report here an original systematic review of the metabolomic studies that have identified putative biomarkers in the context of liver transplantation. Eighteen studies met the inclusion criteria that involved sampling of blood (n = 4), dialysate fluid (n = 4), bile (n = 5), and liver tissue (n = 5). Metabolites of amino acid and nitrogen metabolism, anaerobic glycolysis, lipid breakdown products, and bile acid metabolism were significantly different in transplanted livers with and without graft dysfunction. However, criteria for defining the graft dysfunction varied across studies. This systematic review demonstrates that metabolomics can be deployed in identification of metabolic indicators of graft dysfunction with a view to implicated molecular mechanisms. We conclude the article with a horizon scanning of metabolomics technology in liver transplantation and its future prospects and challenges in research and clinical practice.


High Voltage LiNi0.5Mn1.5O4/Li4Ti5O12 Lithium Ion Cells at Elevated Temperatures: Carbonate- versus Ionic Liquid-Based Electrolytes.
Thanks to its high operating voltage, the LiNi0.5Mn1.5O4 (LNMO) spinel represents a promising next-generation cathode material candidate for Lithium ion batteries. However, LNMO-based full-cells with organic carbonate solvent electrolytes suffer from severe capacity fading issues, associated with electrolyte decomposition and concurrent degradative reactions at the electrode/electrolyte interface, especially at elevated temperatures. As promising alternatives, two selected LiTFSI/pyrrolidinium bis(trifluoromethane-sulfonyl)imide room temperature ionic liquid (RTIL) based electrolytes with inherent thermal stability were investigated in this work. Linear sweep voltammetry (LSV) profiles of the investigated LiTFSI/RTIL electrolytes display much higher oxidative stability compared to the state-of-the-art LiPF6/organic carbonate based electrolyte at elevated temperatures. Cycling performance of the LNMO/Li4Ti5O12 (LTO) full-cells with LiTFSI/RTIL electrolytes reveals remarkable improvements with respect to capacity retention and Coulombic efficiency. Scanning electron microscopy (SEM) images and X-ray diffraction (XRD) patterns indicate maintained pristine morphology and structure of LNMO particles after 50 cycles at 0.5C. The investigated LiTFSI/RTIL based electrolytes outperform the LiPF6/organic carbonate-based electrolyte in terms of cycling performance in LNMO/LTO full-cells at elevated temperatures.


Novel CRK-Cyclin Complex Controls Spindle Assembly Checkpoint in Toxoplasma Endodyogeny.
Opportunistic parasites of the Apicomplexa phylum use a variety of division modes built on two types of cell cycles that incorporate two distinctive mechanisms of mitosis: uncoupled from and coupled to parasite budding. Parasites have evolved novel factors to regulate such unique replication mechanisms that are poorly understood. Here, we have combined genetics, quantitative fluorescence microscopy, and global proteomics approaches to examine endodyogeny in Toxoplasma gondii dividing by mitosis coupled to cytokinesis. In the current study, we focus on the steps controlled by the recently described atypical Cdk-related kinase T. gondii Crk6 (TgCrk6). While inspecting protein complexes, we found that this previously orphaned TgCrk6 kinase interacts with a parasite-specific atypical cyclin, TgCyc1. We built conditional expression models and examined primary cell cycle defects caused by the lack of TgCrk6 or TgCyc1. Quantitative microscopy assays revealed that tachyzoites deficient in either TgCrk6 or the cyclin partner TgCyc1 exhibit identical mitotic defects, suggesting cooperative action of the complex components. Further examination of the mitotic structures indicated that the TgCrk6/TgCyc1 complex regulates metaphase. This novel finding confirms a functional spindle assembly checkpoint (SAC) in T. gondii. Measuring global changes in protein expression and phosphorylation, we found evidence that canonical activities of the Toxoplasma SAC are intertwined with parasite-specific tasks. Analysis of phosphorylation motifs suggests that Toxoplasma metaphase is regulated by CDK, mitogen-activated kinase (MAPK), and Aurora kinases, while the TgCrk6/TgCyc1 complex specifically controls the centromere-associated network. IMPORTANCE The rate of Toxoplasma tachyzoite division directly correlates with the severity of the disease, toxoplasmosis, which affects humans and animals. Thus, a better understanding of the tachyzoite cell cycle would offer much-needed efficient tools to control the acute stage of infection. Although tachyzoites divide by binary division, the cell cycle architecture and regulation differ significantly from the conventional binary fission of their host cells. Unlike the unidirectional conventional cell cycle, the Toxoplasma budding cycle is braided and is regulated by multiple essential Cdk-related kinases (Crks) that emerged in the place of missing conventional cell cycle regulators. How these novel Crks control apicomplexan cell cycles is largely unknown. Here, we have discovered a novel parasite-specific complex, TgCrk6/TgCyc1, that orchestrates a major mitotic event, the spindle assembly checkpoint. We demonstrated that tachyzoites incorporated parasite-specific tasks in the canonical checkpoint functions.


Phase scaling properties of perturbation-induced multistability in a driven nonlinear system.
Phase scaling relations for the onsets of both saddle-node bifurcations and boundary crises induced by resonant periodic perturbations at subharmonic frequencies are found in a period-doubled system from the results of numerical simulation. These phase dependences determine the domains of existence of induced attractors in (bifurcation parameter, perturbation phase) parameter space. The overlapping of these domains leads to the formation of zones with different numbers of coexisting attractors. The numerical evidence was obtained on the basis of single-mode rate equations of a laser with parameters corresponding to a realistic loss-modulated CO2 laser.


SCORPION is a stacking-based ensemble learning framework for accurate prediction of phage virion proteins.
Fast and accurate identification of phage virion proteins (PVPs) would greatly aid facilitation of antibacterial drug discovery and development. Although, several research efforts based on machine learning (ML) methods have been made for in silico identification of PVPs, these methods have certain limitations. Therefore, in this study, we propose a new computational approach, termed SCORPION, (StaCking-based Predictior fOR Phage VIrion PrOteiNs), to accurately identify PVPs using only protein primary sequences. Specifically, we explored comprehensive 13 different feature descriptors from different aspects (i.e., compositional information, composition-transition-distribution information, position-specific information and physicochemical properties) with 10 popular ML algorithms to construct a pool of optimal baseline models. These optimal baseline models were then used to generate probabilistic features (PFs) and considered as a new feature vector. Finally, we utilized a two-step feature selection strategy to determine the optimal PF feature vector and used this feature vector to develop a stacked model (SCORPION). Both tenfold cross-validation and independent test results indicate that SCORPION achieves superior predictive performance than its constitute baseline models and existing methods. We anticipate SCORPION will serve as a useful tool for the cost-effective and large-scale screening of new PVPs. The source codes and datasets for this work are available for downloading in the GitHub repository ( https://github.com/saeed344/SCORPION ).


Clinical review: Anti-TNFalpha therapies in uveitis: perspective on 5 years of clinical experience.
Despite a lack of robust evidence, anti-TNF therapies are in wide use for the treatment of noninfectious ocular inflammatory diseases. There is a clear rationale, based on mechanistic and preclinical efficacy data, for their use in posterior segment intraocular inflammation. However, their increasing use for other indications has been largely extrapolated from the benefit observed in autoinflammatory and autoimmune systemic diseases. Given their cost and the potential for significant adverse events, this review highlights the evidence for their continued use, possibilities for switching anti-TNF agents, and ways of reducing the risk of therapy.


Toroidal grating astigmatism of high-harmonics characterized by EUV Hartmann sensor.
The beam transport of single high-order harmonics in a monochromator arrangement is studied. A toroidal grating combines spectral filtering and focusing in order to produce a small individual spot for each harmonic. Here, the effect of small deviations from perfect alignment is investigated. Experimentally, a Hartmann sensor monitors the EUV wavefront while the grating is subjected to an online alignment procedure. The obtained results are confirmed by a simple theoretical description employing optical matrix methods.


Effects of a preload increase on ventricular filling in coronary artery disease.
This study was conducted to investigate the effects of a preload increase on ventricular filling dynamics in 50 coronary artery disease patients both before and immediately after leg elevation. Mitral and tricuspid peak E and A velocities and the mitral E/A velocity ratio increased after leg elevation whereas isovolumic relaxation time and mitral deceleration time decreased. The increase in tricuspid peak A velocity after leg elevation was related to the positivity of the exercise stress test (p = 0.01). The increase in mitral peak A velocity was related to the history of old myocardial infarction (p = 0.006).


[Extrapulmonary tuberculosis according to the data of personal registries of new tuberculosis cases].
By using the subject registers of new tuberculosis cases, which are kept in the subjects of the Russian Federation within tuberculosis epidemiological monitoring, the authors analyze notified extrapulmonary tuberculosis morbidity in 21 subjects (17,301 patients over 1995-2006). Despite the stability of the pattern of recorded pulmonary tuberculosis (PT) as a whole, great differences are found in the notification rate of different forms of PT between individual subjects of the Russian Federation, there are wide differences in the proportion and absolute number of PT patients first detected in the coterminous subjects of the Russian Federation with similar natural climatic and socioeconomic conditions. The registered patients with PT are shown to be a heterogeneous group of patients who substantially differ in gender, age, and the forms of disease therefore the use of total parameters to assess the situation, by detecting and diagnosing PL, is not efficient.


Expression, purification and crystallization of CLK1 kinase - A potential target for antiviral therapy.
Cdc-like kinase 1 (CLK1) is a dual-specificity kinase capable of autophosphorylation on tyrosine residues and Ser/Thr phosphorylation of its substrates. CLK1 belongs to the CLK kinase family that regulates alternative splicing through phosphorylation of serine-arginine rich (SR) proteins. Recent studies have demonstrated that CLK1 has an important role in the replication of influenza A and chikungunya viruses. Furthermore, CLK1 was found to be relevant for the replication of HIV-1 and the West Nile virus, making CLK1 an interesting cellular candidate for the development of a host-directed antiviral therapy that might be efficient for treatment of newly emerging viruses. We describe here our attempts and detailed procedures to obtain the recombinant kinase domain of CLK1 in suitable amounts for crystallization in complex with specific inhibitors. The key solution for the reproducibility of crystals resides in devising and refining expression and purification protocols leading to homogeneous protein. Co-expression of CLK1 with λ-phosphatase and careful purification has yielded crystals of CLK1 complexed with the KH-CB19 inhibitor that diffracted to 1.65 Å. These results paved the path to the screening of more structures of CLK1 complexed compounds, leading to further optimization of their inhibitory activity. Moreover, since kinases are desired targets in numerous pathologies, the approach we report here, the co-expression of kinases with λ-phosphatase, previously used in other kinases, can be adopted as a general protocol in numerous kinase targets for obtaining reproducible and homogenic non-phosphorylated (inactive) forms suitable for biochemical and structural studies thus facilitating the development of novel inhibitors.


Gain-induced speech distortions and the absence of intelligibility benefit with existing noise-reduction algorithms.
Most noise-reduction algorithms used in hearing aids apply a gain to the noisy envelopes to reduce noise interference. The present study assesses the impact of two types of speech distortion introduced by noise-suppressive gain functions: amplification distortion occurring when the amplitude of the target signal is over-estimated, and attenuation distortion occurring when the target amplitude is under-estimated. Sentences corrupted by steady noise and competing talker were processed through a noise-reduction algorithm and synthesized to contain either amplification distortion, attenuation distortion or both. The attenuation distortion was found to have a minimal effect on speech intelligibility. In fact, substantial improvements (>80 percentage points) in intelligibility, relative to noise-corrupted speech, were obtained when the processed sentences contained only attenuation distortion. When the amplification distortion was limited to be smaller than 6 dB, performance was nearly unaffected in the steady-noise conditions, but was severely degraded in the competing-talker conditions. Overall, the present data suggest that one reason that existing algorithms do not improve speech intelligibility is because they allow amplification distortions in excess of 6 dB. These distortions are shown in this study to be always associated with masker-dominated envelopes and should thus be eliminated.


Evolution of CH3NO2/Si interfacial chemistry under reaction conditions: a combined experimental and theoretical study.
Dissociative adsorption of CH3NO2 onto a Si(100)-2 × 1 surface is studied using ambient-pressure X-ray photoelectron spectroscopy (AP-XPS) and density functional theory (DFT) calculations. The unprecedented scission of the C-N bond in CH3NO2 and the formation of a Si-CH3 surface species are observed at elevated CH3NO2 pressure (0.5 mbar) and temperature (>573 K).


Proteomics of Streptococcus mutans to Reveal the Antibiofilm Formation Mechanism of Ag/ZnO Nanocomposites with Light-Emitting Diode Radiation.
As a biofilm-associated disease, dental caries benefits from nanoparticle (NP)-based therapies. Streptococcus mutans (S. mutans) is a primary aetiologic agent for dental caries development. We successfully applied a synergistic therapy of Ag/ZnO nanocomposites combined with light-emitting diode (LED) radiation to inhibit S. mutans biofilms. However, the antibiofilm mechanism has not been fully elucidated, and little is known about the biofilm formation ability of bacteria that survive NP-based therapies. This study explored the antibiofilm formation mechanism of this synergistic therapy by an integrated approach based upon proteomics. Synergistic therapy killed 99.8% of bacteria, while the biofilm formation ability of 0.2% surviving bacteria was inhibited. The proteomic responses of S. mutans to synergistic therapy were comprehensively characterized to unveil the mechanism of bacterial death and biofilm formation inhibition of the surviving bacteria. In total, 55 differentially expressed proteins (12 upregulated and 43 downregulated) were recorded. The bioinformatic analysis demonstrated that cellular integrity damage and regulated expression of structure-associated proteins were the main reasons for bacterial death. In addition, the proteomic study indicated the potential inhibition of metabolism in surviving bacteria and provided a biofilm-related network consisting of 17 differentially expressed proteins, explaining the multiantibiofilm formation actions. Finally, we reported and verified the inhibitory effects of synergistic therapy on sucrose metabolism and D-alanine metabolism, which disturbed the biofilm formation of surviving bacteria. Our findings demonstrated that synergistic therapy killed most bacteria and inhibited the surviving bacteria from forming biofilms. Furthermore, the antibiofilm formation mechanism was revealed by proteomics analysis of S. mutans after synergistic therapy and subsequent metabolic studies. Our success may provide a showcase to explore the antibiofilm formation mechanism of NP-based therapies using proteomic studies.


The effects of training length on the perceptual learning of time-compressed speech and its generalization.
Brief exposure to time-compressed speech yields both learning and generalization. Whether such learning continues over the course of multi-session training and if so whether it is more or less specific than exposure-induced learning is not clear, because the outcomes of intensive practice with time-compressed speech have rarely been reported. The goal here was to determine whether prolonged training on time-compressed speech yields additional learning and generalization beyond that induced by brief exposure. Listeners practiced the semantic verification of time-compressed sentences for one or three training sessions. Identification of trained and untrained tokens was subsequently compared between listeners who trained for one or three sessions, listeners who were briefly exposed to 20 time-compressed sentences and naive listeners. Trained listeners outperformed the other groups of listeners on the trained condition, but only the group that was trained for three sessions outperformed the other groups when tested with untrained tokens. These findings suggest that although learning of distorted speech can occur rapidly, more stable learning and generalization might be achieved with longer, multi-session practice. It is suggested that the findings are consistent with the framework proposed by the Reverse Hierarchy Theory of perceptual learning.


Protection against intranasal infection of mice with Bordetella pertussis.
Mice have been infected by intranasal instillation of Bordetella pertussis and the infection monitored by determining numbers of bacteria isolated from the lungs. Outer membrane proteins, filamentous hemagglutinin, toxoided-lymphocytosis promoting factor and agglutinogens (fimbriae) actively protect mice against intranasal infection and antibodies of the antigens neutralize infectivity. The neutralization of infection by agglutinins is serospecific. In general, antigens that actively protect mice against intracerebral infections also protect against intranasal infections but some antigens, such as filamentous hemagglutinin and agglutinogens, protect only against intranasal infections. The intranasal protective potency of antigens can be enhanced by including low levels of active lymphocytosis promoting factor in the preparations. The relevance of the intranasal test to the potency testing of pertussis vaccines is discussed.


Effect of Point Defects on Electronic Structure of Monolayer GeS.
Using density functional theory calculations, atomic and electronic structure of defects in monolayer GeS were investigated by focusing on the effects of vacancies and substitutional atoms. We chose group IV or chalcogen elements as substitutional ones, which substitute for Ge or S in GeS. It was found that the bandgap of GeS with substitutional atoms is close to that of pristine GeS, while the bandgap of GeS with Ge or S vacancies was smaller than that of pristine GeS. In terms of formation energy, monolayer GeS with Ge vacancies is more stable than that with S vacancies, and notably GeS with Ge substituted with Sn is most favorable within the range of chemical potential considered. Defects affect the piezoelectric properties depending on vacancies or substitutional atoms. Especially, GeS with substitutional atoms has almost the same piezoelectric stress coefficients eij as pristine GeS while having lower piezoelectric strain coefficients dij  but still much higher than other 2D materials. It is therefore concluded that Sn can effectively heal Ge vacancy in GeS, keeping high piezoelectric strain coefficients.


Bicycle handlebar injury in a nine-year old causing a common hepatic duct tear.
A case in which a handlebar injury to the abdomen resulted in a common hepatic duct tear is presented. This injury has not been previously documented in the literature. The case emphasizes the diverse and potentially serious consequences of handlebar injuries in children, and reminds us that the presentation may be delayed.


N-isobutyloxycarbonylation for improved detection of 3'-hydroxystanozolol and its 17-epimer in doping control.
An improved screening method was developed for 3'-hydroxystanozolol and its 17-epimer in human urine involving gas chromatography-mass spectrometry (GC-MS) with N-isobutyloxycarbonyl (isoBOC) and O-trimethylsilyl (TMS) derivatization. A procedure was reported previously for the pentane extraction of many steroids from urine in doping control, but it was not suitable for the detection of stanozolol metabolites. Compared with the n-pentane extraction method, which gave a poor recovery (< 10%), isoBOC extraction resulted in a good recovery (> 80%). The sensitivity and specificity of mixed N-isoBOC-O-TMS derivatization were adequate for the detection of 3'-hydroxystanozolol and its 17-epimer when 3 ml of urine was used with spiking at a level of 2 ng ml-1. When applied to a stanozolol-positive urine sample, the proposed method allowed rapid and sensitive screening for the detection of 3'-hydroxystanozolol and its 17-epimer.


Speech characteristics in individuals with myasthenia gravis: a case control study.
Myasthenia Gravis (MG) is an autoimmune disease. The characteristic symptoms of the disease are muscle weakness and fatigue. These symptoms affect de oral muscles causing dysarthria, affecting about 60% of patients with disease progression. Describe the speech pattern of patients with MG and comparing with healthy controls (HC). Case-control study. Participants were divided in MG group (MGG) with 38 patients MG diagnosed and HC with 18 individuals matched for age and sex. MGG was evaluated with clinical and motor scales and answered self-perceived questionnaires. Speech assessment of both groups included: recording of speech tasks, acoustic and auditory-perceptual analysis. In the MGG, 68.24% of the patients were female, with average age of 50.21 years old (±16.47), 14.18 years (±9.52) of disease duration and a motor scale of 11.19 points (±8.79). The auditory-perceptual analysis verified that 47.36% (n = 18) participants in MGG presented mild dysarthria, 10.52% (n = 4) moderate dysarthria, with a high percentage of alterations in phonation (95.2%) and breathing (52.63%). The acoustic analysis verified a change in phonation, with significantly higher shimmer values in the MGG compared to the HC and articulation with a significant difference between the groups for the first formant of the /iu/ (p = <.001). No correlation was found between the diagnosis of speech disorder and the dysarthria self-perception questionnaire. We found dysarthria mild in MG patients with changes in the motor bases phonation and breathing, with no correlation with severity and disease duration.


Tramadol/acetaminophen combination tablets for the treatment of osteoarthritis flare pain: a multicenter, outpatient, randomized, double-blind, placebo-controlled, parallel-group, add-on study.
In a flare of osteoarthritis (OA) pain, increasing the dose of standard anti-inflammatory or routine analgesic drugs may not be practical because of an increased incidence of side effects. In patients achieving inadequate pain relief from traditional non-steroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase (COX)-2-selective inhibitors, it may be appropriate to add an analgesic agent with a different mechanism of action, thereby targeting multiple components of the pain pathway. The addition of tramadol/acetaminophen tablets to existing therapy was compared with the addition of placebo in the treatment of OA flare pain. This was a multicenter, outpatient, randomized, double-blind, placebo-controlled, parallel-group, add-on study. Patients received 1 or 2 tramadol/acetaminophen (37.5 mg/325 mg) tablets QID or matching placebo for 10 days in addition to ongoing NSAID or COX-2-selective inhibitor therapy. The primary outcome measures were average daily pain intensity and average daily pain relief scores from days 1 through 5. Three hundred eight patients were randomized to tramadoUacetaminophen (n = 197) or placebo (n = 111) and were followed for up to 10 days. Patients had a mean (+/-SD) age of 60.1 +/- 9.87 years, and were predominantly female (71.8%) and white (87.7%). Their mean (+/- SD) pain visual analog score at baseline was 73.2 +/- 11.8 mm, and their mean pain intensity score was 2.4 +/- 0.5 (on a scale from 0 = none to 3 = severe). Average daily pain intensity and pain relief scores were significantly improved with tramadol/acetaminophen compared with placebo on the primary assessment of efficacy from days 1 through 5 (both, P < 0.001) and on the assessment of efficacy from days I through 10 (both, P < 0.001) Tramadol/acetaminophen was significantly superior to placebo on the patients' and physicians' overall assessments of medication (both, P < 0.001) and on 3 of 4 subscales (pain [P = 0.004], physical function [P = 0.013], and overall [P = 0.008]) of the Western Ontario and McMaster Universities Osteoarthritis Index Questionnaire. The most common treatment-emergent adverse events with tramadol/acetaminophen were nausea, vomiting, and dizziness. No serious adverse events were reported in the tramadol/acetaminophen group. In this study, addition of tramadol/acetaminophen to NSAID or COX-2-selective inhibitor therapy was well tolerated and effective in the treatment of OA flare pain.


Mechanisms of PCBs mixture toxicity on isolated rat hepatocytes.
Exposure of isolated hepatocytes to a polychlorinated biphenyl mixture induced a rapid loss of cell viability. The effect was not dose-dependent. The biochemical effects in the cellular toxicity did not involve glutathione content, protein sulfhydryl groups and lipid peroxidation. A transient increase in cytosolic Ca2+ was observed after exposing the hepatocytes to the polychlorinated biphenyl mixture. Our findings indicate that polychlorinated biphenyls are able to kill hepatocytes and suggest that elevation of cytosolic Ca2+ concentration could be responsable of the toxicity.


Factor Xa-evoked relaxation in rat aorta: involvement of PAR-2.
Protease-activated receptor-2 (PAR-2) and/or effector cell protease receptor-1 (EPR-1) may mediate the direct cellular actions of coagulation factor Xa in some cultured cell lines. The present study examined if factor Xa could actually evoke relaxation through either of these receptor systems in isolated rat aorta. Factor Xa at 8.5-85 nM, like the PAR-2-activators trypsin and SLIGRL-NH(2), produced nitric oxide-dependent relaxation in the precontracted aortic rings. PAR-2 desensitization abolished relaxation responses to factor Xa as well as trypsin in the rings. The factor Xa interepidermal growth factor synthetic peptide L(83)FTRKL(88)(G)-NH(2), known to block factor Xa binding to EPR-1, failed to inhibit factor Xa-evoked relaxation in the preparations. Our findings provide evidence that factor Xa evokes relaxation by activating PAR-2, but independently of EPR-1, in the rat aorta. The factor Xa-PAR-2 pathway might thus contribute to the severe hypotension during sepsis, in which multiple coagulation factors including factor X would become activated and PAR-2 would be induced.


Microfistulas Causing Diverse Regional Ischemia: Consecutive Inferior and Lateral ST-Elevation Myocardial Infarction.
Coronary artery fistulas (CAFs) are described as abnormal communications between a coronary artery and cardiac chambers, or other vascular structures. The two types of CAFs are defined as type I (singular fistula) and type II (microfistulas). Even though various electrocardiographic changes have been previously described in CAF patients, coronary-artery microfistulas causing ST-segment elevation in diverse locations have not been reported. We describe a case report of an adult patient who presented with acute inferior myocardial infarction due to coronary-artery microfistulas. During the hospital stay, the patient re-experienced chest pain, and control electrocardiography revealed ST-segment elevation in the I and AVL leads along with reciprocal ST-segment depression in the inferior precordial leads. Although CAFs are clinically rare, they can have important clinical consequences. Microfistulas should be kept in mind as a cause of ST elevation myocardial infarction in some patients.


Detection and implications of a time-reversal breaking state in underdoped cuprates.
We present general symmetry considerations on how a time-reversal breaking state may be detected by angle-resolved photoemission using circularly polarized photons as has been proposed earlier. Results of recent experiments utilizing the proposal in underdoped cuprates are analyzed and found to be consistent in their symmetry and magnitude with a theory of the copper oxides. These experiments if correct, together with evidence of a quantum critical point and marginal Fermi-liquid properties near optimum doping, suggest that the essentials of a valid microscopic theory of the phenomena in the cuprates may have been found.


Minimal alveolar concentration of sevoflurane inhibiting the reflex pupillary dilatation after noxious stimulation in children and young adults.
In children, sevoflurane is the most commonly used anaesthetic. Its excellent haemodynamic tolerance gives it a wide therapeutic index. This halogenated agent can abolish movement [minimal alveolar concentration (MAC)] or haemodynamic responses (MACBAR) to noxious stimulus in children as in adults. Reflex pupillary dilatation (RPD) has been demonstrated as a very sensitive measure of noxious stimulation. In order to investigate the effect of sevoflurane on the RPD, a subcortical reflex, we determined the MAC of sevoflurane inhibiting the RPD in 50% of the subjects in response to skin incision (MACpup) in pre- and post-pubertal subjects. We included 30 pre-pubertal children and 19 post-pubertal subjects. Patients received sevoflurane at preselected concentrations according to an 'up and down' design, and after a steady-state period, skin incision was performed. The RPD was considered as significant when the pupillary diameter increased by more than 100%. Heart rate (HR) and bispectral index (BIS) changes were analysed according to the pupillary response. The MACpup of sevoflurane was 4.8% (95% confidence interval, 4.6-5.1%) in pre-pubertal children vs 3.4% (3.5-3.3%) in post-pubertal subjects (P<0.001). Inhibition of RPD was always associated with lack of significant HR response. In pre-pubertal children receiving high concentrations of sevoflurane, RPD in response to noxious stimulation was frequently associated with lack of HR response and low BIS values. MACpup was higher than MAC and close to the MACBAR. Inhibition of RPD in pre-pubertal children required higher sevoflurane concentrations compared with post-pubertal subjects, suggesting that the relationship between the brain structure sensitivities may differ with brain maturation.


Intramolecular charge transfer of 4-(dimethylamino)benzonitrile probed by time-resolved fluorescence and transient absorption: No evidence for two ICT states and a pisigma( *) reaction intermediate.
For the double exponential fluorescence decays of the locally excited (LE) and intramolecular charge transfer (ICT) states of 4-(dimethylamino)benzonitrile (DMABN) in acetonitrile (MeCN) the same times tau(1) and tau(2) are observed. This means that the reversible LE<==>ICT reaction, starting from the initially excited LE state, can be adequately described by a two state mechanism. The most important factor responsible for the sometimes experimentally observed differences in the nanosecond decay time, with tau(1)(LE)<tau(1)(ICT), is photoproduct formation. By employing a global analysis of the LE and ICT fluorescence response functions with a time resolution of 0.5 ps/channel in 1200 channels reliable kinetic and thermodynamic data can be obtained. The arguments presented in the literature in favor of a pisigma( *) state with a bent CN group as an intermediate in the ICT reaction of DMABN are discussed. From the appearance of an excited state absorption (ESA) band in the spectral region between 700 and 800 nm in MeCN for N,N-dimethylanilines with CN, Br, F, CF(3), and C(=O)OC(2)H(2) p-substituents, it is concluded that this ESA band cannot be attributed to a pisigma( *) state, as only the C-C[Triple Bond]N group can undergo the required 120 degrees bending.


Enantioselective, Stereodivergent Hydroazidation and Hydroamination of Allenes Catalyzed by Acyclic Diaminocarbene (ADC) Gold(I) Complexes.
The gold-catalyzed enantioselective hydroazidation and hydroamination reactions of allenes are presented herein. ADC gold(I) catalysts derived from BINAM were critical for achieving high levels of enantioselectivity in both transformations. The sense of enantioinduction is reversed for the two different nucleophiles, allowing access to both enantiomers of the corresponding allylic amines using the same catalyst enantiomer.


[The role of computer tomography in the diagnosis of aneurysms of the abdominal aorta].
The advantages of computer tomography are obvious. They include the non-invasive character of examination, the detection of aneurysms with a small diameter and the opportunity to check them systematically. Computer tomography is in the authors' opinion most effective in the differential diagnosis and for the assessment of the character of aneurysms--stable or unstable, and in particular in the diagnosis of initial stages of ruptures.


Initiation, desistance, and persistence of men's sexual coercion.
Patterns of sexually coercive behavior were examined among 266 Asian American and 299 European American men over 1 year. Noncoercer (n = 358), desister (n = 120), initiator (n = 39), and persistent (n = 48) sexually coercive groups were identified. The strongest predictor of sexual coercion was past sexual coercion. Persistent sexual coercers were higher than the other groups in delinquency and hostile masculinity and were nearly twice as likely to engage in laboratory sexual harassment. Loss of face attenuated self-reported sexual coercion and laboratory sexual harassment risk among Asian Americans and attenuated only laboratory sexual harassment risk among European Americans. These findings suggest that the heterogeneity of sexually coercive behavior and ethnicity are important research and clinical considerations.


[From anthropocentrism to ecocentrism: educating for ecological care in health].
The focus of the paper is the meaning of ecological care as understood by students and educators and how this issue is addressed in programs in the fields of health sciences and health care in a federal public institution in southern Brazil. Our goal is to discuss the central category. The methodology adopted was Grounded Theory. Ten interviews were carried out among two sample groups between September, 2008, and April, 2009. The results led to the design of the theory: considering ecological care as broad and complex phenomenon, and the core category: the ecological care that results from relations, interactions and associations within the global environment. We concluded that rejecting anthropocentrism is not enough for the survival of all forms of life in the planet. This survival demands educating for ecocentrism and for systemic-functional interactivity and adaptability. We must go beyond speeches and world conferences and redo the web of interdependence of all beings and elements of nature.


Right 25 bp terminus sequence of the nopaline T-DNA is essential for and determines direction of DNA transfer from agrobacterium to the plant genome.
We have determined which sequences at the right border of the T-DNA region of the nopaline C58 Ti plasmid are required for transfer and/or integration of the T-DNA into the plant cell genome. The results indicate that the 25 bp T-DNA terminus repeat sequence, TGACAGGATATATTGGCGGGTAAAC, is directly responsible for T-DNA transfer; furthermore, this sequence is directional in its mode of action. A transfer-negative nononcogenic Ti plasmid derivative, pGV3852, was constructed, in which 3 kb covering the right T-DNA border region was substituted for by pBR322 sequences. The pBR322 sequences in pGV3852 provide a site for homologous recombination with pBR-derived plasmids containing sequences to assay for transfer activity. First, a 3.3 kb restriction fragment overlapping the deleted region in pGV3852 was shown to restore transfer activity. Second, a sequence of only 25 bp, the T-DNA terminus sequence, was shown to be sufficient to restore normal transfer activity. The transfer-promoting sequences are most active when reinserted in one orientation, that normally found in the Ti plasmid.


The complete chloroplast genome of Prunus campanulata 'Fugui' (Rosaceae).
Prunus campanulata 'Fugui' is newly bred cultivar. Here, we report its complete chloroplast genome. The length of the P. campanulata 'Fugui' chloroplast genome is 157,948 bp, with a large single-copy region of 85,948 bp, a small single-copy region of 19,128 bp and a pair of inverted repeat regions of 26,436 bp each. The genome contains 90 protein-coding genes, 65 transfer RNA genes and 9 ribosomal RNA genes. In addition, the genome contains 67 simple sequence repeats. Phylogenetic analysis revealed that P. campanulata 'Fugui' is genetically related to previously reported P. campanulata.


Congestive heart failure. Considerations for primary care physicians.
Initial evaluation of congestive heart failure (CHF) should emphasize a search for curable and precipitating causes. Echocardiography is mandatory if CHF is a serious consideration after initial evaluation. Digitalis, diuretics, and vasodilators in the form of angiotensin-converting enzyme (ACE) inhibitors are the mainstays of pharmacologic therapy. Early use of ACE inhibitors for asymptomatic left ventricular dysfunction and established CHF lessens morbidity and mortality. The number of expensive hospitalizations can be reduced by patient education and institution of a flexible therapeutic program guided by the patient's symptoms and daily weigh-ins.


Prognostic values of aldehyde dehydrogenase 1 isoenzymes in ovarian cancer.
Aldehyde dehydrogenase 1 (ALDH1) activity has been used as a functional stem cell marker to isolate cancer stem cells in different cancer types, including ovarian cancer. However, which ALDH1's isoenzymes are contributing to ALDH1 activity in ovarian cancer remains elusive. In addition, the prognostic value of an individual ALDH1 isoenzyme in ovarian cancer is not clear. Thus, we accessed the prognostic value of ALDH1 isoenzymes in ovarian cancer patients through the "Kaplan-Meier plotter" online database, which can be used to determine the effect of the genes on ovarian cancer prognosis. We found that high mRNA expression of five ALDH1 isoenzymes, such as ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, and ALDH1L1, was not correlated with overall survival (OS) for all 1,306 ovarian cancer patients. In addition, all five of the ALDH1 isoenzymes' high mRNA expression was found to be uncorrelated with OS in serous cancer or endometrioid cancer patients. However, ALDH1A3's high mRNA expression is associated with worse OS in grade II ovarian cancer patients, hazard ratio (HR) 1.53 (1.14-2.07), P=0.005. ALDH1A2's high mRNA expression is significantly associated with worse OS in TP53 wild-type ovarian cancer patients, HR 2.86 (1.56-5.08), P=0.00036. In addition, ALDH1A3's high mRNA expression is significantly associated with better OS in TP53 wild-type ovarian cancer patients, HR 0.56 (0.32-1.00), P=0.04. Our results indicate that although ALDH1 isoenzyme mRNA might not be a prognostic marker for overall ovarian cancer patients, some isoenzymes, such as ALDH1A2 and ALDH1A3, might be a good prognostic marker for some types of ovarian cancer patients.


An assessment of burn prevention knowledge in a high burn-risk environment: restaurants.
Our facility has seen an increase in the number of cases of children burned in restaurants. Fieldwork has revealed many unsafe serving practices in restaurants in our tristate area. The current research targets what appears to be an underexamined burn-risk environment, restaurants, to examine server knowledge about burn prevention and burn care with customers. Participants included 71 local restaurant servers and 53 servers from various restaurants who were recruited from undergraduate courses. All participants completed a brief demographic form as well as a Burn Knowledge Questionnaire. It was found that server knowledge was low (ie, less than 50% accuracy). Yet, most servers reported that they felt customer burn safety was important enough to change the way that they serve. Additionally, it was found that length of time employed as a server was a significant predictor of servers' burn knowledge (ie, more years serving associated with higher knowledge). Finally, individual items were examined to identify potential targets for developing prevention programs.


Synthesis of a biological active tumor growth factor from the predicted DNA sequence of Shope fibroma virus.
A 55-residue peptide comprising the carboxyl portion (residues 26-80) of the Shope fibroma virus growth factor (SFGF), a predicted 80-residue DNA virus gene product that encoded a homologous sequence with the epidermal growth factor transforming growth factor alpha family, was synthesized by a stepwise solid-phase method. The synthetic SFGF (26-80) purified to homogeneity by reverse-phase HPLC was characterized by fission ionization mass spectrometry and amino acid analysis. The disulfide pairings were established by enzymatic digestion and mass spectrometry and were found to be similar to those of EGF and TGF alpha. Synthetic SFGF (26-80) was found to share about 10% of the activities as EGF in the radioreceptor binding to A431 cells, stimulation of [3H]thymidine uptake in NRK cells, and induction of colony formation in soft-agar assay. Our results therefore confirmed that SFGF contained the putative biological activities of the EGF-TGF alpha family and that production of SFGF by Shope fibroma virus infected cells may account for the proliferative diseases associated with this particular virus.