Identification of a hard surface contact-induced gene in Colletotrichum gloeosporioides conidia as a sterol glycosyl transferase, a novel fungal virulence factor.
Hard surface contact has been known to be necessary to induce infection structure (appressorium) formation in many phytopathogenic fungi. However, the molecular basis of this requirement is unknown. We have used a differential display approach to clone some of the genes induced in the conidia by hard surface contact. We report that one of the genes induced by hard-surface contact of the conidia of Colletotrichum gloeosporioides, chip6, encodes a protein with homology to sterol glycosyl transferases. chip6 expressed in E. coli catalyses glucosyl transfer from UDP-glucose to cholesterol. Disruption of chip6 causes a marked decrease in the transferase activity and a drastic reduction in virulence on its natural host, avocado fruits, although the mutant is capable of normal growth and appressorium formation. The requirement for sterol glycosyl transferase for pathogenicity suggests a novel biological function for this transferase.


Brain inspired path planning algorithms for drones.
With the development of artificial intelligence and brain science, brain-inspired navigation and path planning has attracted widespread attention. In this paper, we present a place cell based path planning algorithm that utilizes spiking neural network (SNN) to create efficient routes for drones. First, place cells are characterized by the leaky integrate-and-fire (LIF) neuron model. Then, the connection weights between neurons are trained by spike-timing-dependent plasticity (STDP) learning rules. Afterwards, a synaptic vector field is created to avoid obstacles and to find the shortest path. Finally, simulation experiments both in a Python simulation environment and in an Unreal Engine environment are conducted to evaluate the validity of the algorithms. Experiment results demonstrate the validity, its robustness and the computational speed of the proposed model.


Prevalence of faecal-borne parasites in colony stray cats in northern Italy.
Endoparasitic infections are common in stray cats. Many of these parasites are responsible for zoonoses, and stray cats can be a source of environmental contamination. The prevalence of parasites in 139 stray colony cats in the city of Milan, northern Italy, was investigated by faecal examination. The overall prevalence of endoparasites was 50.4%, with 11 different parasites found. Parasites with zoonotic potential were detected in 49.6% of cats. Concurrent infections with two or more zoonotic parasites were recorded in 14.3% of cats. Among the parasites found, the most common was Toxocara cati (33.1%; P <0.0001). The other species found by coproscopic examination were: Ancylostoma tubaeformae (7.2%), Isospora species (4.3%), Trichuris vulpis (2.9%), Dipylidium caninum (2.9%), Aelurostrongylus abstrusus (2.9%), Eucoleus aerophilus (syn Capillaria aerophila) (1.4%), Spirometra species (1.4%), Taenia pisiformis (0.7%) and Hymenolepis nana (0.7%). Coproantigen specific for Giardia duodenalis was detected in 2.9% of the samples. Pseudoparasites (eggs of mites) were found in 4.3% of the samples. No sample contained Toxoplasma gondii oocysts, despite the fact that 70 cats tested positive for T gondii-specific IgG antibodies, and none of the diarrhoetic samples tested positive for Cryptosporidium species oocysts. Variables linked to infection were body condition score (BCS), the presence of diarrhoea and infection with G duodenalis. Cats infected with G duodenalis were more likely to have a low BCS (odds ratio (OR) = 11.5, P = 0.02) and diarrhoea (OR = 30.7, P = 0.0007). The results of the present study confirm that endoparasitic infections, most of which have zoonotic potential, are distributed in stray colony cats of Milan.


Heat shock factor 1 is a powerful multifaceted modifier of carcinogenesis.
Heat shock factor 1 (HSF1) is the master regulator of the heat shock response in eukaryotes, a very highly conserved protective mechanism. HSF1 function increases survival under a great many pathophysiological conditions. How it might be involved in malignancy remains largely unexplored. We report that eliminating HSF1 protects mice from tumors induced by mutations of the RAS oncogene or a hot spot mutation in the tumor suppressor p53. In cell culture, HSF1 supports malignant transformation by orchestrating a network of core cellular functions including proliferation, survival, protein synthesis, and glucose metabolism. The striking effects of HSF1 on oncogenic transformation are not limited to mouse systems or tumor initiation; human cancer lines of diverse origins show much greater dependence on HSF1 function to maintain proliferation and survival than their nontransformed counterparts. While it enhances organismal survival and longevity under most circumstances, HSF1 has the opposite effect in supporting the lethal phenomenon of cancer.


Relation between aortic knob width and subclinical left ventricular dysfunction in hypertensive patients.
The assessment of left ventricular (LV) structure and function is important in the evaluation of hypertensive heart disease, as it provides information on the cardiovascular morbidity and mortality. Aortic knob width (AKW) is a measurement of radiographic structure formed by the foreshortened aortic arch and a portion of the descending aorta. The main aim of this study was to investigate the relation between AKW on the routine chest radiography and subclinical LV dysfunction in hypertensive patients. A total of 144 patients with hypertension admitted to the cardiology outpatients clinic were enrolled consecutively. The patients were divided into two groups according to tissue Doppler-derived myocardial performance index (MPI): subclinical LV dysfunction group (abnormal MPI ≥ 0.5, n = 85) and absence of subclinical LV dysfunction group (normal MPI< 0.5, n = 59). Patients with subclinical LV dysfunction were older (60 ± 8 vs. 54 ± 8, p = 0.001). Left ventricular mass index (LVMI) (96 ± 27 vs. 74 ± 24, p < 0.001) and prevalence of LV hypertrophy (28 vs. 8%, p = 0.011) were significantly different between two groups. Patients with subclinical LV dysfunction had higher AKW (42 ± 6 vs. 34 ± 5, p < 0.001) compared with patients without subclinical LV dysfunction. There was a significant correlation between MPI and AKW (r = 0.7, p < 0.001). Multiple logistic regression analysis showed that AKW (β = 0.617, p = 0.001) and posterior wall thickness (PWth) (β = 1.189, p = 0.021) were independently associated with subclinical LV dysfunction. Analysis using the Receiver Operating Characteristic (ROC) curve has demonstrated that aortic knob of 37 mm constitutes the cutoff value for the presence of subclinical LV dysfunction with 85.9% sensitivity and 86.4% specificity (The Area under the Curve ± Standard Error (AUC±SE) = 0.916 ± 0.024, p < 0.001). AKW may provide important predictive information on subclinical LV dysfunction in patients with hypertension.


Synthesis of oligosaccharides related to galactomannans from Aspergillus fumigatus and their NMR spectral data.
The synthesis of model oligosaccharides related to antigenic galactomannans of the dangerous fungal pathogen Aspergillus fumigatus has been performed employing pyranoside-into-furanoside (PIF) rearrangement and controlled O(5) → O(6) benzoyl migration as key synthetic methods. The prepared compounds along with some previously synthesized oligosaccharides were studied by NMR spectroscopy with the full assignment of 1H and 13C signals and the determination of 13C NMR glycosylation effects. The obtained NMR database on 13C NMR chemical shifts for oligosaccharides representing galactomannan fragments forms the basis for further structural analysis of galactomannan related polysaccharides by a non-destructive approach based on the calculation of the 13C NMR spectra of polysaccharides by additive schemes.


Resection of meningiomas with implantable microwave coagulation.
Implantable microwave coagulation was used to perform resection on 62 patients that had intracranial meningiomas. When 20-60 W microwave power was applied for 15 s, the temperature at the center of the tumor tissue was 43-63 degrees C; 30 mm from the center, the temperature was under 40 degrees C. Histological changes in the center of the tumor showed coagulative necrosis, diminished nuclei, and obliterated blood vessels. The changes at 10-20 mm from the center of the tumor showed coagulative necrosis and degeneration and, 30-50 mm from the center of the tumor, showed normal cell morphology after microwave coagulation. The thermal field in brain tumor has an effective diameter of about 40 mm. No side effects on the normal brain tissues were observed. The amount of blood loss during the operation was minimal while the meningioma was coagulated, especially when the meningioma was located at the skull base or in the parasagittal or cerebral convexity region. After microwave coagulation, the entire tumor could easily be removed. Among the 62 surgically treated cases, gross total tumor excision was 85 percent. No postoperative complications occurred after microwave coagulation, and there was no operative mortality in the series. We believe that this new technique has the advantage of simplicity, less blood loss, and smooth postoperative procedures. Hemostatic effects during the operation are satisfactory, and blood transfusion can be reduced by 50-60 percent.


"Life is about trying to find a better place to live": Discourses of dwelling in a pro-recovery suicide forum.
In the two decades since the advent of Web 2.0, scholars of cybersuicide have identified many beneficial and harmful uses of the internet. However, the discursive meanings interactionally created by suicide website users have scarcely been attended to. The present study uses the theory and method of cultural discourse analysis (CuDA) to arrive at meanings about place that radiate from online communication among users of SuicideForum.com (SF), a pro-recovery website. Analyses of 2,119 posts across 131 threads reveal two overarching discursive themes. The first speaks to problematic discourses about place, including the role of placelessness and entrapment in the genesis of suicidality and its affective states, leading to further diminution of experiential worlds. The second theme taps into participants' notions of what constitutes safe spaces, such as the presence of empathetic others who respect one's timetable for personal disclosure, and the freedom to experiment with new ways of inhabiting the world. The study has numerous implications for clinical practice, including recasting psychological disturbances in terms of self-world relations and reconsidering involuntary psychiatric hospitalization in light of forum participants' preoccupation with entrapment.


Student and community outcomes in service-learning: part 2--community outcomes.
This article is the second of a two-part series reporting outcomes from a service-learning program implemented in a bachelor of science in nursing program. Part 1 (on pages 512-515) described students' perceptions of outcomes realized from the program, and Part 2 describes the community outcomes. The purposes of the program were to provide students with history-taking, blood pressure, and heart rate assessment skills, and beginning counseling skills, as well as to provide the university community with blood pressure screening and counseling in a convenient and accessible location. Data on community outcomes were collected on a continual basis during the hypertension screening and counseling program implementation. Clients were anonymously surveyed on health behavior actions taken after their screening and on the screening process. More than 700 client screenings were performed over 2 years, with positive health behavior changes being reported by clients.


Total Synthesis of (-)-Isoschizogamine.
The total synthesis of (-)-isoschizogamine was accomplished, featuring the construction of the quaternary carbon center by the modified Johnson-Claisen rearrangement in basic media and the facile assembly of the key tetracyclic quinolone intermediate through a cascade cyclization. The characteristic cyclic aminal was constructed by late-stage C-H functionalization at the position adjacent to the lactam nitrogen using a combination of CrO3 and nBu4 NIO4 and subsequent Bi(OTf)3 -mediated cyclization.


Improving comprehension of medication information: implications for nurse-patient communication.
Older adults with chronic illness have complex medication regimens that require an understanding of a wide range of information. The impact of patient characteristics (e.g., cognitive ability), health documents (language and multimedia), and the communication context (available time to communicate) in which older adults understand the information needed to take medication safely are considered to identify recommendations for nurses to communicate effectively with older adults. This article focuses on visually presented information (text and graphics) to motivate suggestions for improving patient education materials. Information communicated during provider-patient encounters is also considered, with implications for improving nurse-patient collaboration.


[Prolactin--significance in benign and malignant breast diseases].
At present, the role of prolactin has not yet been precisely determined both in the development and in the progression of benign and malignant diseases of the breast. Experimental investigations and data of the human receptor assay have clearly indicated the initial and promoting activity of prolactin in the genesis of breast tumors. However, the data published so far, which is in some cases highly contradictory, does not allow a positive appraisal on the correlation of the prolactin level and breast diseases in clinical research and experimental studies. The studies still to be carried out in human medicine with precise definition of the TRH-prolactin-target cell axis compared with the proof of the receptor radioimmunoassay in healthy and malignant breast tissue which has still not yet been provided might give rise to rather more clarity in this rather manifold problem.


Anatomy of the proximal coronary arteries as a risk factor in primary repair of common arterial trunk.
The objective of this study was to investigate whether the proximal coronary arterial anatomy is a risk factor in surgical treatment of common arterial trunk, with special focus on the value of preoperative angiocardiography. A retrospective analysis was performed of all 22 patients who underwent primary surgical repair of the common arterial trunk, with a mean follow-up of 5.1 years. In 18 patients preoperative angiocardiography was performed. Anatomical features (angiocardiographical, surgical as well as post-mortem) of the proximal coronary arteries were investigated. With standard biplane angiocardiography single and dual coronary arterial systems could adequately be distinguished. However, the position of the coronary orifices in relation to the sinus of Valsalva could not adequately be identified. Three patients had coronary abnormalities without surgical consequences. In 2 cases the surgical approach had to be modified due to the coronary anatomy. Early mortality was 23% (5/22) and was correlated with worse functional class (p < 0.05) and earlier date of operation (p < 0.05). Late mortality was 5% (1/22). Five patients were reoperated, without mortality. Fourteen surviving patients are in functional class I, and 2 in class II. A further improvement of the surgical therapy of common arterial trunk might be provided by adequate appreciation of the proximal coronary arterial anatomy at surgery.


Universal slip dynamics in metallic glasses and granular matter - linking frictional weakening with inertial effects.
Slowly strained solids deform via intermittent slips that exhibit a material-independent critical size distribution. Here, by comparing two disparate systems - granular materials and bulk metallic glasses - we show evidence that not only the statistics of slips but also their dynamics are remarkably similar, i.e. independent of the microscopic details of the material. By resolving and comparing the full time evolution of avalanches in bulk metallic glasses and granular materials, we uncover a regime of universal deformation dynamics. We experimentally verify the predicted universal scaling functions for the dynamics of individual avalanches in both systems, and show that both the slip statistics and dynamics are independent of the scale and details of the material structure and interactions, thus settling a long-standing debate as to whether or not the claim of universality includes only the slip statistics or also the slip dynamics. The results imply that the frictional weakening in granular materials and the interplay of damping, weakening and inertial effects in bulk metallic glasses have strikingly similar effects on the slip dynamics. These results are important for transferring experimental results across scales and material structures in a single theory of deformation dynamics.


Emerging malnutrition during hospitalisation independently predicts poor 3-month outcomes after acute stroke: data from a Chinese cohort.
Questions exist regarding the causal relationship between malnutrition and stroke outcomes. This study aimed to determine whether nutritional status changes or malnutrition during hospitalisation could predict 3-month outcomes in acute stroke patients. During a 10-month period, patients who suffered their first stroke within 7 days after stroke onset were included in this prospective multi-centre study. The demographic parameters, stroke risk and severity factors, malnutrition risk factors and dysphagia were recorded. Nutritional status was assessed by 3 anthropometric and 3 biochemical indices. Changes in nutritional status were defined by comparing the admission values with the 2-week values. A Modified Rankin Scale score of 3-6 was defined as a poor outcome at the 3-month follow-up. Univariate and multiple logistic regression analyses were used to investigate the power of nutritional status changes in predicting poor patient outcomes. Data from 760 patients were analysed. Poor outcomes were observed in 264 (34.7%) patients. Malnutrition prevalence was 3.8% at admission and 7.5% after 2-weeks in hospital, which could not predict 3-month outcome. Emerging malnutrition was observed in 36 patients (4.7%) during the 2-week hospitalisation period and independently predicted poor 3-month outcomes after adjusting for confounding factors (odds ratio 1.37, 95% confidence interval 1.03-1.83). Emerging malnutrition during hospitalisation independently predicted poor 3-month outcomes in acute stroke patients in this study.


Exclusive Breastfeeding in the Bronx-Successes and Shortcomings.
Despite efforts to encourage breastfeeding, exclusive breastfeeding (EBF) rates in the Bronx remain suboptimal. Hospital restrictions and uncertainty surrounding the side effects of coronavirus disease 2019 (COVID-19) greatly impacted the mother-infant dyad during the postpartum hospitalization. Preliminary studies found an initial decrease in EBF, but lasting effects remain unknown. This study aimed to investigate the effect of the COVID-19 pandemic on birth hospitalization EBF rates among a high-risk urban patient population. A retrospective chart review was conducted on all newborns admitted to the newborn nursery at an urban medical center between 2019 and 2021. Patients were separated into prepandemic and pandemic cohorts. Patient demographics, maternal comorbidities, length of stay, feeding method, and newborn characteristics, including status as high risk for hypoglycemia, were collected. EBF was defined as receiving only mother's milk during the birth hospitalization. Descriptive statistics and bivariate analysis were used to examine the data. A total of 630 prepandemic and 643 pandemic newborns were included. The cohorts did not differ in baseline maternal characteristics. Prepandemic newborns were less likely to be high risk (23.3 vs. 29.4%, p = 0.01), more likely to see the hospital lactation consultant (53.2 vs. 24.0%, p < 0.001), and had a longer average length of stay (63.4 vs. 54.5 hours, p < 0.001). Most infants in both cohorts received some breastmilk during the hospitalization (97.6 vs. 94.6%, not significant). There was no difference in EBF between cohorts among all newborns (9.5 vs. 11.4%, p = 0.29) or among nonhigh-risk newborns (12.2 vs. 15.0%, p = 0.22). EBF rates in the Bronx, NY did not change during the pandemic period, despite an increase in high-risk newborns. Further investigation into the effect of lactation consultation, maternal race, ethnicity, and primary language should be further explored to understand the implications of health care disparities on the mother-infant dyad. · The COVID-19 pandemic disrupted many aspects of the mother-infant dyad.. · EBF rates at an urban institution in the Bronx did not change during the COVID-19 pandemic.. · Further investigation is warranted to better understand the barriers to EBF in this population..


Home care triage nurse.
As a TN who began in a position with little insight into the expectations and who has been able to develop the system into one that ideally meets the needs of our home care institution, I always feel challenged. Initially, my concern was that I would lose touch with what was new and would lose my clinical skills. To the contrary, I feel that I have honed my skills. By understanding the steps to procedures and their rationale, disease processes, symptoms, treatment regimes, and through continuing education, I have become confident in teaching patients and caregivers over the phone. Although the staff includes those in each of our branches, I am able to have contact with them all now more than ever. Because we known as home care workers that it is difficult to develop relationships and trust among staff members because of the independent nature of home care nursing, forging a relationship based on trust between the staff members and the TN is crucial for delivering consistent patient care 24 hours a day, 7 days a week. It is note-worthy that to develop the TN system effectively, I was granted autonomy and lent support by the agency administration and management. This autonomy continues to be instrumental for success.


Synthetic Extracellular Volume in Cardiac Magnetic Resonance Without Blood Sampling: a Reliable Tool to Replace Conventional Extracellular Volume.
The calculation of extracellular volume (ECV) in cardiac magnetic resonance requires hematocrit, limiting its applicability in clinical practice. Based on the linear relationship between hematocrit and blood T1 relaxivity, a synthetic ECV could be estimated without a blood sample. We aim to develop and test regression models for synthetic ECV without blood sampling in 1.5-T and 3.0-T scanners. A total of 1101 subjects who underwent cardiac magnetic resonance scanning with native and postcontrast T1 mapping and venous hematocrit within 24 hours were retrospectively enrolled. Subjects were randomly split into derivation (n=550) and validation (n=551) subgroups for each scanner. Different regression models were derived controlling for sex, field strength, and left ventricle/right ventricle blood pool and validated in the validation group. We performed additional validation analyses in subgroups of patients with histological validation (n=17), amyloidosis (n=29), anemia (n=185), and reduced ejection fraction (n=322). In the derivation group, 8 specific models and 2 common estimate models were derived. In the validation group, using specific models, synthetic ECV had high agreement with conventional ECV (R2, 0.87; P<0.0001 and R2, 0.88, P<0.0001; -0.16% and -0.10%, left ventricle and right ventricle model, respectively). Common models also performed well (R2, 0.88; P<0.0001 and R2, 0.89, P<0.0001; -0.21% and -0.18%, left ventricle and right ventricle model, respectively). Histological validation demonstrated equal performance of synthetic and measured ECV. Synthetic ECV as calculated by the common model showed a bias in the anemia cohort significantly reduced by the specific model (-2.45 to -1.28, right ventricle common and specific model, respectively). Synthetic ECV provided a promising way to calculate ECV without blood sampling. Specific models could provide the most accurate value, while common models could be more suitable in routine clinical practice because of their simplicity while maintaining adequate accuracy.


Giant-cell tumor of bone arising from the falx cerebri. A case report.
The histological and ultrastructural features of a giant-cell tumor of bone arising in the falx cerebri of a 27 year-old man are described. The tumor was embedded in the medial aspect of the left frontal lobe and was not attached to any of the bones of the skull. At surgery, the tumor was lightly adherent to the falx and was easily extracted. Histologically, the tumor was composed of mononuclear spindle-shaped and ovoid stromal cells, multinuclear giant cells containing 20-30 nuclei, and foci of osteoid and bone production. Hemorrhagic and cystic areas were also present within the tumor. Ultrastructurally, the spindle-shaped cells resembled fibroblasts and were surrounded by small bundles of collagen fibrils. The ovoid cells contained numerous mitochondria, abundant rough endoplasmic reticulum, vesicles, lysosomes, phagosomes and osseous material in the cytoplasm suggesting their monocyte-macrophage lineage. These cells were closely apposed and displayed evidence of fusion in the form of focal and linear subplasmalemmal densities to form multinucleated giant cells with similar organelles and multiple nuclei. It is suggested that the primary giant cell tumor of the one arose from the metaplastic ossification of the falx. To our knowledge, a giant-cell tumor of bone arising from the falx cerebri has not been previously described.


Primary care for diabetes mellitus patients from the perspective of the care model for chronic conditions.
to assess the health care Primary Health Care professionals provide to diabetes mellitus patients from the perspective of the Modelo de Atenção às Condições Crônicas. qualitative study, using the theoretical framework of Complex Thinking and the Modelo de Atenção às Condições Crônicas and the methodological framework of assessment research. To collect the data, 38 interviews were held with health professionals and managers; observation of the activities by the health teams; and analysis of 25 files of people who received this care. The data analysis was supported by the software ATLAS.ti, using the directed content analysis technique. at the micro level, care was distant from the integrality of the actions needed to assist people with chronic conditions and was centered on the biomedical model. At the meso level, there was disarticulation among the professionals of the Family Health Strategy, between them and the users, family and community. At the macro level, there was a lack of guiding strategies to implement public policies for diabetes in care practice. the implementation of the Modelo de Atenção às Condições Crônicas represents a great challenge, mainly needing professionals and managers who are prepared to work with chronic conditions are who are open to break with the traditional model.


The chemical senses and nutrition in older adults.
Taste and smell are critical to dietary selection, especially for older adults, whose appetite is reduced. Neuroimaging studies can elucidate the process that causes the decrease of chemosensory functions with aging. The profound lost of olfactory functions in persons with Alzheimer disease accentuate the problem of inadequate food intake and disease progression.


SOCIAL SUPPORT, PSYCHOLOGICAL DISTRESS, AND PARENTING STRAINS IN MOTHERS OF VERY LOW BIRTHWEIGHT INFANTS.
This study investigated maternal psychological distress, perceptions of social supports, and parenting strains after the birth of a very low birthweight (VLBW) infant. Compared to mothers of term infants, mothers of VLBW infants had significantly higher incidence of psychological distress during the neonatal period, but did not differ from mothers of term infants in their feelings of role restriction, parenting competence, or social supports. Lower general social support predicted high distress levels, but only for mothers of VLBW infants. Mothers with a low sense of parenting competence, but support from spouse/partners reported lower maternal distress.


Reduction of spasticity in cerebral palsy using feedback of the tonic stretch reflex: a controlled study.
Subjects with cerebral palsy aged six to 19 years undertook a training programme to reduce spasticity and contracture of the triceps surae muscle using feedback of the gain of the tonic stretch reflex. Stretch reflex gain was significantly reduced (by 50 per cent on average) in all eight test subjects, whereas there was no significant change in control subjects, matched for age and level of spasticity, who had no reflex training. Contracture of the triceps surae muscle was not altered. Since the reduction in spasticity can be expected to slow the recurrence of muscle shortening, it is suggested that for correction of muscle contracture, muscle-lengthening procedures to promote muscle growth should be combined with reflex training to maintain the growth achieved.


Speech breathing: variable but individual over time and according to limb movements.
Breathing is variable but also highly individual. Since the 1980s, evidence of a ventilatory personality has been observed in different physiological studies. This original term refers to within-speaker consistency in breathing characteristics across days or even years. Speech breathing is a specific way to control ventilation while supporting speech planning and phonation constraints. It is highly variable between speakers but also for the same speaker, depending on utterance properties, bodily actions, and the context of an interaction. Can we yet still observe consistency over time in speakers' breathing profiles despite these variations? We addressed this question by analyzing the breathing profiles of 25 native speakers of German performing a narrative task on 2 days under different limb movement conditions. The individuality of breathing profiles over conditions and days was assessed by adopting methods used in physiological studies that investigated a ventilatory personality. Our results suggest that speaker-specific breathing profiles in a narrative task are maintained over days and that they stay consistent despite light physical activity. These results are discussed with a focus on better understanding what speech breathing individuality is, how it can be assessed, and the types of research perspectives that this concept opens up.


Taxonomy of the Capensibufo rosei group (Anura: Bufonidae) from South Africa.
A molecular and morphological study of the Mountain Toadlets, previously included in Capensibufo rosei, showed that there are several previously unrecognised species in this group. We describe three new species from the Hawekwas, Hottentots-Holland, Groenland and Riviersonderend Mountains; the DuToitskloof Mountains, and the Akkedis, Koeël and Kleinriviers Mountains, South Africa. Capensibufo rosei is restricted to the Table Mountain chain of the Cape Peninsula.


Photon-manipulated drug release from a mesoporous nanocontainer controlled by azobenzene-modified nucleic acid.
Herein a photon-manipulated mesoporous release system was constructed based on azobenzene-modified nucleic acids. In this system, the azobenzene-incorporated DNA double strands were immobilized at the pore mouth of mesoporous silica nanoparticles. The photoisomerization of azobenzene induced dehybridization/hybridization switch of complementary DNA, causing uncapping/capping of pore gates of mesoporous silica. This nanoplatform permits holding of guest molecules within the nanopores under visible light but releases them when light wavelength turns to the UV range. These DNA/mesoporous silica hybrid nanostructures were exploited as carriers for the cancer cell chemotherapy drug doxorubicin (DOX) due to its stimuli-responsive property as well as good biocompatibility via MTT assay. It is found that the drug release behavior is light-wavelength-sensitive. Switching of the light from visible to the UV range uncapped the pores, causing the release of DOX from the mesoporous silica nanospheres and an obvious cytotoxic effect on cancer cells. We envision that this photocontrolled drug release system could find potential applications in cancer therapy.


Deep learning quantification of vascular pharmacokinetic parameters in mouse brain tumor models.
Dynamic contrast-enhanced (DCE) MRI is widely used to assess vascular perfusion and permeability in cancer. In small animal applications, conventional modeling of pharmacokinetic (PK) parameters from DCE MRI images is complex and time consuming. This study is aimed at developing a deep learning approach to fully automate the generation of kinetic parameter maps, Ktrans (volume transfer coefficient) and Vp (blood plasma volume ratio), as a potential surrogate to conventional PK modeling in mouse brain tumor models based on DCE MRI. Using a 7T MRI, DCE MRI was conducted in U87 glioma xenografts growing orthotopically in nude mice. Vascular permeability Ktrans and Vp maps were generated using the classical Tofts model as well as the extended-Tofts model. These vascular permeability maps were then processed as target images to a twenty-four layer convolutional neural network (CNN). The CNN was trained on T1-weighted DCE images as source images and designed with parallel dual pathways to capture multiscale features. Furthermore, we performed a transfer study of this glioma trained CNN on a breast cancer brain metastasis (BCBM) mouse model to assess the potential of the network for alternative brain tumors. Our data showed a good match for both Ktrans and Vp maps generated between the target PK parameter maps and the respective CNN maps for gliomas. Pixel-by-pixel analysis revealed intratumoral heterogeneous permeability, which was consistent between the CNN and PK models. The utility of the deep learning approach was further demonstrated in the transfer study of BCBM. Because of its rapid and accurate estimation of vascular PK parameters directly from the DCE dynamic images without complex mathematical modeling, the deep learning approach can serve as an efficient tool to assess tumor vascular permeability to facilitate small animal brain tumor research.


Soft particle model for block copolymers.
A soft particle model for diblock (AB) copolymer melts is proposed. Each molecule is mapped onto two soft spheres built by Gaussian A- and B-monomer distributions. An approximate analytical expression for the joint distribution function for the distance between both spheres and their radii of gyration is derived, which determines the entropic contribution to the intramolecular free energy. Adding a mean-field expression for the intermolecular interactions, we obtain the total free energy of the system. Based on this free energy, Monte Carlo simulations are carried out to study the kinetics of microphase ordering in the bulk and its effect on molecular diffusion. This is followed by an analysis of thin films, with emphasis on pattern transfer from walls with a periodic structure. It is shown that the level of coarse graining in the soft particle model is suitable to describe structural and kinetic properties of copolymers on mesoscopic scales.


Altered peripheral profile of blood cells in Alzheimer disease: A hospital-based case-control study.
Alzheimer disease (AD) has been made a global priority for its multifactorial pathogenesis and lack of disease-modifying therapies. We sought to investigate the changes of profile of blood routine in AD and its correlation with the disease severity.In all, 92 AD patients and 84 age and sex-matched normal controls were enrolled and their profiles of blood routine were evaluated.Alzheimer disease patients had increased levels of mean corpuscular hemoglobin, mean corpuscular volume, red cell distribution width-standard deviation, mean platelet volume,and decreased levels of platelet distribution width, red blood cell, hematocrit, hemoglobin, lymphocyte, and basophil compared with normal controls.Alterations in quantity and quality of blood cells may be involved in the pathogenesis of AD and contribute to the disease progression.


Right heart pulmonary embolism in transit: a review of therapeutic considerations.
Two patients with pulmonary emboli and right heart masses detected on echocardiography are described. One patient underwent successful surgical embolectomy and the other was successfully treated with intravenous thrombolysis. Both were alive and well at six months' follow-up. The presence of a right heart clot in the setting of pulmonary emboli carries a very high mortality rate and warrants urgent therapy, which may include anticoagulation, thrombolysis or surgical embolectomy. Because limited information is available, therapy must be individualized based on patient characteristics, clot location and local expertise. The pertinent literature is reviewed and relevant issues in decision making are discussed.


Evaluation of 2-week repeated oral dose toxicity of 100 nm zinc oxide nanoparticles in rats.
The aim of this study was to verify subacute oral dose toxicity of positively charged 100 nm zinc oxide (ZnO(AE100[+])) nanoparticles (NPs) in Sprague-Dawley rats. ZnO(AE100[+]) NPs were administered to rats of each sex by gavage at 0, 500, 1,000, and 2,000 mg/kg/day for 14 days. During the study period, clinical signs, mortality, body weight, food consumption, hematology, serum biochemistry, gross pathology, organ weight, and histopathology were examined. Increased mortality and clinical signs, decreased body weight, feed consumption, hemoglobin (HB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet (PT), and lymphocyte (LYM) and increased white blood cells (WBCs), neutrophils (NEUs), alkaline phosphatase (ALP), and histopathological alterations in the spleen, stomach, and pancreas were observed at 2,000 mg/kg/day. Increased clinical signs, decreased body weight, feed consumption, HB, HCT, MCV, MCH, MCHC, and LYM and increased WBCs, NEUs, ALP, and histopathological alterations in the spleen, stomach, and pancreas were seen at 1,000 mg/kg/day. Increased clinical signs, decreased MCV and MCH and increased histopathological alterations in the stomach and pancreas were found at 500 mg/kg/day. These results suggest that the target organs were the spleen, stomach, and pancreas in rats. The no-observed-adverse-effect level was <500 mg/kg for both sexes.


Bradycardia in toluene poisoning.
Tachyarrhythmias are the classical manifestation of toluene cardiotoxicity. The presumed mechanism is sensitization of the myocardium to the potential arrhythmogenic effect of endogenous catecholamines, occasionally resulting in fatality. Bradyarrhythmias have been repeatedly shown in animal models, but have been reported only once in a human. Two patients with toluene intoxication presented with severe sinus bradycardia. One patient had also atrial-ventricular dissociation. In both cases cardiac rhythm returned to normal within several hours. We suggest that the spectrum of cardiotoxic symptoms associated with toluene intoxication in humans includes bradyarrhythmias as well as tachyarryhthmias.


Experimental white piedra: a robust approach to ultrastructural analysis, scanning electron microscopy and etiological discoveries.
White piedra is a fungal infection characterized by nodules comprised of Trichosporon species and restricted to the extrafollicular portion of the hair shaft. The diagnosis is based on clinical and mycological characteristics, and must be confirmed with a precise identification of the etiological agent. This research aimed to develop an in vitro infection model of white piedra and analyze its morphological and ultra-structural aspects. In the process, hair infection was induced using eight isolates of the genus Trichosporon maintained in the Culture Collection Micoteca URM. The ITS and IGS1 regions were sequenced for taxonomic confirmation. Scanning Electron Microscope (SEM) was performed at the Strategic Center for Northeast Technologies (CETENE). The scanning electron microscope was equipped with an Energy Dispersion Spectrometer (EDS). The Trichosporon isolates were identified as Trichosporon asahii (6) and Trichosporon montevideense (2) by internal transcript spacer (ITS) region and intergenic spacer 1 region (IGS1) sequencing. All eight strains were used to induce the in vitro hair infection, and nodules formed after the incubation period. Temperature variations and high humidity were not observed to be related to the development of this hair disease. The main chemical constituents detected in the nodules were carbon, nitrogen and oxygen, as well as a low level of sulfur. The absence of calcium, combined with the low level of sulfur, might explain the soft nature of the white piedra nodules. This study demonstrated that several Trichosporon species may be responsible for causing white piedra.


Microinjection of rat GH but not human IGF-I into a defined area of the hypothalamus inhibits endogenous GH secretion in rats.
It has been surmised that GH exerts feedback action on the hypothalamus and thereby regulates its own secretion. Our previous studies suggested that GH acts on somatostatin neurons in the hypothalamic periventricular nucleus (PeV) and neuropeptide Y (NPY) neurons in the hypothalamic arcuate nucleus (ARC). However, there remains uncertainty whether GH acts directly or indirectly through the generation of IGFs on the hypothalamus to regulate its own secretion. To examine this, rat GH (rGH) or human IGF-I was injected directly into a defined area of the hypothalamus, and the blood GH profile was observed in conscious male rats. In the rats given 0.5 microgram rGH into the ARC or PeV bilaterally, GH secretion was inhibited, and the inhibition lasted for 12 h. During the period of inhibition, the duration and amplitude of GH pulses were significantly decreased and the episodic secretion of GH appeared irregularly compared with the vehicle-injected control rats. In control rats given the vehicle or those given rGH into the lateral hypothalamus, the blood GH profile did not change and pulsatile GH secretion was produced every 3 h. When 0.1 microgram IGF-I was injected into the ARC or PeV bilaterally, the blood GH secretory pattern was not affected. Together with the results of our previous studies showing that c-fos gene expression was induced by systemic administration of GH and that GH receptor mRNA was contained in somatostatin neurons in the PeV and NPY neurons in the ARC, the data of the present study indicate that GH, but not IGF-I, acts on the cells in the ARC and the PeV or in their vicinity to inhibit its own secretion, presumably by activating the somatostatin and NPY neurons.


Regulation of the human leukemia inhibitory factor gene by ETS transcription factors.
Leukemia inhibitory factor (LIF) is a pleiotropic cytokine mainly produced by activated T lymphocytes. We previously demonstrated that human Jurkat T lymphoma cells represent a valid model of LIF gene expression. This study was designed to identify regions critical for LIF promoter activation in Jurkat cells. Luciferase constructs under the control of different portions of the human LIF promoter were transfected into Jurkat cells, and promoter activity was determined by luminometry. Similar experiments were performed with constructs bearing mutations in the putative ETS binding regions in the LIF promoter. RT-PCR, Western blot and gelshift experiments were performed to study expression and DNA binding of ETS factors in lymphoid cells. With the exception of the shortest construct not including the putative ETS binding sites, all wildtype LIF promoter constructs were strongly inducible by phorbol ester/ionomycin. In contrast, the mutant constructs were significantly less inducible. Cotransfection of the wild-type constructs with ETS expression vectors resulted in significant enhancement of promoter activity. ets-1 and ets-2 mRNA and protein were shown to be expressed in Jurkat cells. Gelshift experiments revealed that proteins present in nuclear extracts from Jurkat cells specifically bind to both artificial ETS consensus sites and ETS binding sites present in the LIF promoter. We conclude that binding of ETS transcription factors to the ETS binding sites in the human LIF promoter is critical for its inducibility in response to T cell activators. ETS transcription factors thus play an important functional role within the endocrine-immune network.


Continuous monitoring of intracranial pressure in severe closed head injury without mass lesions.
Intracranial pressure (ICP) was monitored continuously for up to two weeks in 40 patients with severe closed head injury with no angiographic evidence of mass lesion. Two-thirds of these patients had normal pressure. The results indicated that there is a lack of correlation between clinical presentation and ICP. Reliable prognostic factors include clinical evidence of brain stem dysfunction and age, but not intracranial pressure. From the data we have concluded that the clinical value of ICP monitoring in this type of head injury is uncertain.


The use of TrkA-PathHunter assay in high-throughput screening to identify compounds that affect nerve growth factor signaling.
The TrkA-PathHunter cell-based assay was used in high-throughput screening (HTS) to identify compounds that inhibit nerve growth factor (NGF)/TrkA signaling. The assay was conducted in a 384-well format, and typical Z' values during HTS ranged from 0.3 to 0.8. The reproducibility of IC50 values was good, and the use of cryopreserved cells was well tolerated, as judged by assay parameters such as Z' and S/B and by comparison of IC50 values obtained with cells in culture. During hit deconvolution, TrkA-kinase inhibitors were identified with ATP-competitive as well as non-ATP-competitive mechanisms of action. Furthermore, other mechanisms of action such as NGF and TrkA antagonists were also identified. Because of the different molecular mechanisms identified, it is possible that subsequent optimization work to increase affinity and selectivity might lead to compounds that could have a better chance to evoke clinical efficacy without the adverse effects observed for nonselective TrkA inhibitors.


Dynamic relationship between infantile hepatitis syndrome and cytomegalovirus infection.
We investigated the correlation between cytomegalovirus (CMV) infection and infantile hepatitis syndrome and the correlation between blood ammonia levels in children with CMV-induced hepatitis syndrome and liver function indicators. To analyze the relationship between the positive-negative attributes of CMV infection and the recurrence rate of infantile hepatitis syndrome, a total of 86 cases of children with hepatitis syndrome admitted to Xuzhou Children's Hospital from January 2014 to March 2015 were selected for the study group. Furthermore, 86 cases of healthy children who visited our hospital for a physical examination during the same period were selected as the control group. From the two groups, serum CMV-immunoglobulin M (IgM) levels were determined via enzyme-linked immunosorbent assay, and urinary CMV-deoxyribonucleic acid (DNA) was ascertained by fluorescent ratio polymerase chain reaction. These levels were then compared between the two groups and analyzed. A fully automatic biochemical analyzer was utilized to evaluate the blood ammonia and liver function indicators of the children with infantile hepatitis syndrome induced by CMV infection and to analyze the correlation of these factors. A mean follow-up of 12 months after the children's discharge was adopted to observe the relationship between the negative-positive attributes of CMV infection and the recurrence rate in the children upon cure. The positive detection rate for the serum CMV-IgM was 24.4%, and that for the urinary CMV-DNA was 34.9%; both values were significantly higher than that for the control group (P<0.05). The blood ammonia levels of the children with infantile hepatitis syndrome induced by CMV infection were not correlated with the liver function indicators, such as total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, total bile acid, and cholinesterase (P>0.05), but they were negatively correlated with blood albumin (ALB) (P<0.05). The recurrence rate of hepatitis syndrome among the children with negative CMV infection was 3.8%, which was significantly lower than that among the children with positive CMV infection (62.5%, P<0.05). A significant correlation was found between CMV infection and infantile hepatitis syndrome, with the former being a risk factor for the latter. Changes in the conditions of infantile hepatitis syndrome may be reflected by blood ammonia and ALB indicators. Through improved monitoring, these indicators facilitate the early diagnosis and treatment of children with hepatitis syndrome induced by CMV infection. Sufficient attention should be paid to preventive measures to reduce the incidence rate of infantile hepatitis syndrome.


Microfluidic Tensiometry Technique for the Characterization of the Interfacial Tension between Immiscible Liquids.
The interfacial tension between two immiscible fluids is of critical importance for understanding many natural phenomena as well as in industrial production processes; however, it can be challenging to measure this parameter with high accuracy. Most commonly used techniques have significant shortcomings because of their reliance on other data such as density or viscosity. To overcome these issues, we devise a technique that works with very small sample quantities and does not require any data about either fluid, based on micropipette aspiration techniques. The method facilitates the generation of a droplet of one fluid inside of the other, followed by immediate in situ aspiration of the droplet into a constricted channel. A modified Young-Laplace equation is then used to relate the pressure needed to produce a given deformation of the droplet's radius to the interfacial tension. We demonstrate this technique on different systems with interfacial tensions ranging from sub-millinewton per meter to several hundred millinewton per meter, thus over 4 orders of magnitude, obtaining precise results in agreement with the literature solely from experimental observations of the droplet deformation.


Effect of lipid materials on the production of lipase by Torulopsis ernobii.
The yeast Torulopsis ernobii produced approximately 50 units of extracellular lipase (glycerol ester hydrolase, E.C. 184.108.40.206) per ml when grown in 30-liter fermentors at 33 C for 40 hr in a base medium at pH 5.0. The addition of fats, oils, triglycerides, or higher fatty acids to this medium at concentrations of 0.2 to 0.6% markedly increased production; twofold increases in yield were obtained when 0.2% olive oil or a mixture of 0.14% oleic acid and 0.04% palmitic acid was added. The production of lipase paralleled growth, and the role of lipid materials in augmenting lipase production appears to be related to cell growth.


Functional brain imaging in neuropsychology over the past 25 years.
Outline effects of functional neuroimaging on neuropsychology over the past 25 years. Functional neuroimaging methods and studies will be described that provide a historical context, offer examples of the utility of neuroimaging in specific domains, and discuss the limitations and future directions of neuroimaging in neuropsychology. Tracking the history of publications on functional neuroimaging related to neuropsychology indicates early involvement of neuropsychologists in the development of these methodologies. Initial progress in neuropsychological application of functional neuroimaging has been hampered by costs and the exposure to ionizing radiation. With rapid evolution of functional methods-in particular functional MRI (fMRI)-neuroimaging has profoundly transformed our knowledge of the brain. Its current applications span the spectrum of normative development to clinical applications. The field is moving toward applying sophisticated statistical approaches that will help elucidate distinct neural activation networks associated with specific behavioral domains. The impact of functional neuroimaging on clinical neuropsychology is more circumscribed, but the prospects remain enticing. The theoretical insights and empirical findings of functional neuroimaging have been led by many neuropsychologists and have transformed the field of behavioral neuroscience. Thus far they have had limited effects on the clinical practices of neuropsychologists. Perhaps it is time to add training in functional neuroimaging to the clinical neuropsychologist's toolkit and from there to the clinic or bedside. (PsycINFO Database Record


Seasonal survey of contaminants (Cd and Hg) and micronutrients (Cu and Zn) in edible tissues of cephalopods from Tunisia: assessment of risk and nutritional benefits.
Concentrations of cadmium (Cd), copper (Cu), mercury (Hg), and zinc (Zn) were determined by atomic absorption spectrophotometry in the muscle tissues (arms and mantle) of 3 commercial cephalopods (Loligo vulgaris, Octopus vulgaris, and Sepia officinalis) caught in 3 different Tunisian coastal regions. The highest concentrations found correspond to the essential elements Cu and Zn. Octopuses and cuttlefish showed the highest levels of those elements whereas squid presented with significantly higher values of Hg in both muscular tissues. This may be related to different feeding behavior and detoxification processes among benthic and pelagic cephalopods. Variation of element concentrations between seasons was different between species and seemed to be mostly dependent on the sampling site. From a public health standpoint, average concentrations of Cd, Cu, Hg, and Zn measured in edible tissues of cephalopods from this study did not reveal, in general, any risk for consumers. The estimated target hazard quotients for Cd and Hg for consumers of the selected species were below 1 and within the safety range for human health. Moreover, their consumption could provide in an important contribution to the daily dietary intake of Cu for the Tunisian population, especially regarding the consumption of octopus and cuttlefish muscles.


QRS waveform of ventricular extrasystoles and their differentiation from aberrant conduction.
Horizontal and frontal plane QRS loops of patients in sinus rhythm with uniform ventricular extrasystoles were constructed from digitised Frank orthogonal electrocardiogram. In 4 patients ventricular extrasystoles were indistinguishable from right bundle-branch complexes, and in another 4 from left bundle-branch complexes. In 25 patients ventricular extrasystoles showed an initial delay (greater than or equal to 20 msec) of the QRS, followed by an R loop, which in 13 patients resembled LBBB complexes, and 12 patients resembled RBBB complexes with an anterior clockwise loop in the horizontal plane. However, the frontal plane loop was often atypical of either RBBB or LBBB. In 51 patients ventricular extraplane loop was often atypical of either RBBB or LBBB. In 51 patients ventricular extrasystoles and an initial delay which was prolonged into the efferent limb of the QRS loop with acceleration of the afferent limb and/or the QRS loop was directed anteriorly, inferiorly and to the left. Conventional recordings of these extrasystoles usually showed an initial slow upstroke (or downstroke) of the QRS resembling a delta wave. It is suggested that extrasystoles resembling bundle-branch complexes arise close to the main bundle branches but that the other extrasystoles arise at the Purkinje-myocardial junction. Identification and differentiation of ventricular extrasystoles from aberrant conduction is aided by vectorcardiography.


Roles of aqueous nonsolvents influencing the dynamic stability of poly-(n-butyl methacrylate) thin films at biologically relevant temperatures.
Poly-(n-butyl methacrylate) (PnBMA) is an important polymer in biomedical applications. Here we study the stability of PnBMA thin films prepared on top of slippery silicon substrates and exposed to nonsolvent aqueous incubation media like water and phosphate-buffered saline (PBS) at temperatures relevant to biological applications (37 °C, 25 °C and 4 °C). Dewetting hole growth experiments allowed us to probe the instability in PnBMA films upon incubation followed by thermal annealing. From the early stage of dewetting hole growth dynamics, we inferred that the stability of the thin PnBMA films decreases as a function of the duration and temperature of incubation, even though the films were found not to readily dewet at room temperature after incubation. It is also observed that water incubation makes films more unstable than incubation in PBS. We explained our observations as a combined effect of (i) an increase in surface energy of the PnBMA film due to incubation, (ii) an increased destabilizing effect due to the dominant polar interactions between the incubation medium and the PnBMA film and (iii) the plasticization effect of PnBMA films by the incubation media. Plasticization resulted in a decrease in the modulus of PnBMA thin films as a function of incubation time. The viscosity of PnBMA films upon incubation was found to be coupled to the decreasing modulus. Thus we infer that incubation in common aqueous nonsolvents can detrimentally affect the stability of polymers limiting their specific usages through a complex interplay of multiple molecular level phenomena.


Neuroprotective effect of aqueous extract of Selaginella delicatula as evidenced by abrogation of rotenone-induced motor deficits, oxidative dysfunctions, and neurotoxicity in mice.
Oxidative stress is one of the mechanisms implicated to play a significant role in the pathophysiology of Parkinson's disease. Previously, we showed that an aqueous extract of Selaginella delicatula (SDAE) offered robust neuroprotection against rotenone (ROT) in a Drosophila model. In furtherance in the present study, we validated the neuroprotective efficacy of SDAE in a chronic ROT exposure model in mice. Initially, we assessed the propensity of SDAE to modulate the levels of endogenous markers in striatal region of mice. Subsequently, the neuroprotective efficacy of SDAE (100 mg/kg bw, 21 d) to mitigate ROT-induced striatal motor deficits, oxidative stress, and neurotoxicity was examined employing a co-exposure paradigm. We found significant attenuation of ROT-induced motor deficits (stride length and landing foot spread distance) among mice given SDAE supplements. Biochemical analysis revealed that ROT-induced elevation in the levels of oxidative markers in cytosol/mitochondria of striatum were normalized with SDAE supplements. In addition, SDAE also restored the ROT-induced elevation in the levels of oxidized and nitrated proteins. Further, SDAE also restored the activities of acetylcholinesterase and butyrylcholinesterase indicating its effect on cholinergic function. While ROT exposure caused significant perturbations in the activity levels of mitochondrial electron transport chain enzymes (complex I/II), membrane potential and activity of ATPases, these functions were restored to normalcy among mice receiving SDAE suggesting its effects on mitochondrial function. Since these data corroborate our previous findings in Drosophila system, we propose that the neuroprotective property of SDAE may be largely attributed to the antioxidant properties and its ability to attenuate mitochondrial dysfunction. However, studies employing dopaminergic cell models would enable us to identify specific molecular mechanism, by which SDAE exerts neuroprotective action.


Molecular Dynamics Study of Combustion Reactions in a Supercritical Environment. Part 2: Boxed MD Study of CO + OH → CO2 + H Reaction Kinetics.
Oxy-fuel combustion technology holds a great promise in both increasing the efficiency of the energy conversion and reducing environmental impact. However, effects of the higher pressures and replacement of the nitrogen with carbon dioxide diluent are not well understood at present. The title reaction is one of the most important processes in combustion. Despite numerous studies, the effects of supercritical carbon dioxide environment did not receive much attention in the past. Here we report the results of boxed molecular dynamics simulations of these effects at QM/MM theory level with periodical boundary conditions. The free energy barriers for HOCO intermediate formation and decomposition were tabulated in a wide range of pressures (1-1000 atm) and temperatures (400-1600 K). Pressure dependence of calculated rate constants for these reaction steps and overall reaction were analyzed. We found that the CO2 environment may increase these rate constants up to a factor of 25, at near critical conditions. At higher temperatures, this effect weakens significantly. Numerical values for parameters of extended Arrhenius equation, suitable for combustion kinetic modeling are reported.


Patterns of Care and Survival for Elderly Acute Myeloid Leukemia-Challenges and Opportunities.
Acute myeloid leukemia (AML) is a disease of the elderly, with a median age of diagnosis in the sixth decade of life. Mortality has declined over the last few years, but this impact is apparent only in the young, fit AML population. Outcomes for the elderly remain poor, with less than 20% 5-year overall survival rates. Hence, there is an unmet need to identify treatment strategies to maximize benefit in this age group. Elderly AML is a difficult entity to treat due to both disease and patient-related factors. Treatment of this group has a lot of inter-physician and inter-institutional variability. Several objective criteria to assess biological age, impact of co-morbidities, and fitness have been published, which could be utilized to make management decisions. For old and unfit AML patients, a variety of novel therapeutic agents are currently being investigated. Objective analysis of biological age should include assessment of fitness, frailty, and co-morbidities in elderly AML. Future areas of research include development of an objective risk-based approach and its validation in clinical trials, development of novel therapeutic agents, and improvement in supportive care measures.


Efficient method to characterize the context-dependent hydrophobicity of proteins.
Characterizing the hydrophobicity of a protein surface is relevant to understanding and quantifying its interactions with ligands, other proteins, and extended interfaces. However, the hydrophobicity of a complex, heterogeneous protein surface depends not only on the chemistry of the underlying amino acids but also on the precise chemical pattern and topographical context presented by the surface. Characterization of such context-dependent hydrophobicity at nanoscale resolution is a nontrivial task. The free energy, μ(v)(ex), of forming a cavity near a surface has been shown to be a robust measure of context-dependent hydrophobicity, with more favorable μ(v)(ex) values suggesting hydrophobic regions. However, estimating μ(v)(ex) for cavities significantly larger than the size of a methane molecule in a spatially resolved manner near proteins is a computationally daunting task. Here, we present a new method for estimating μ(v)(ex) that is 2 orders of magnitude more efficient than conventional techniques. Our method envisions cavity creation as the emptying of a volume of interest, v, by applying an external potential that is proportional to the number of water molecules, N(v), in v. We show that the "force" to be integrated to obtain μ(v)(ex) is simply the average of N(v) in the presence of the potential, and can be sampled accurately using short simulations (50-100 ps), making our method very efficient. By leveraging the efficiency of the method to calculate μ(v)(ex) at various locations in the hydration shell of the protein, hydrophobin II, we are able to construct a hydrophobicity map of the protein that accounts for topographical and chemical context. Interestingly, we find that the map is also dependent on the shape and size of v, suggesting an "observer context" in mapping the hydrophobicity of protein surfaces.


Ratio of the Primers Used in Polymerase Chain Reaction-Stop Analysis Impacts the Resultant Banding Pattern.
G-quadruplex (G4), as a dynamic nucleic acid secondary structure, widely exists in organism genomes and plays regulatory roles in a variety of cellular functions. Polymerase chain reaction stop assay (PCR-Stop) is a simple, quick, and low-cost widely used method for detection of the binding between G4 and its binding compounds. Different from the common PCR approach, no double-stranded DNA template is needed in the PCR-Stop assay, in which the forward and reverse primers extend against each other in the presence of DNA polymerase to produce a single DNA product. However, unexpected results, such as two or more PCR products, are often generated, and the mechanism is unclear. We found that the ratio of pair primers significantly impacts the generation and components of PCR-Stop products, which is crucial for the interpretation of the experiment results.


MiRNA-329 targeting E2F1 inhibits cell proliferation in glioma cells.
MicroRNAs have recently emerged as key regulators of cancers, miR-329 located on 14q32.31 is one of down-regulated miRNAs in glioma, but the function and molecular mechanisms of miR-329 in determining the malignant phenotype of human glioma are elusive. This study therefore was conducted to investigate the role of miR-329 in biological behaviors of human glioma LN18 and T98G cell lines and its molecular mechanisms. Nine patients with GBM were analyzed for the expression of miR-329 by quantitative RT-PCR. MiR-329 overexpression was established by transfecting miR-329 precursor into LN18 and T98G cells, and its effects on cell proliferation were studied using MTT assay, anchorage-independent growth ability assay, colony formation assays, Bromodeoxyuridine labeling and immunofluorescence.The effects of miR-329 on cell cycle were studied by flow cytometry. The target of miR-329 was determined by luciferase assays. The regulation of miR-329 on Akt pathway was determined by western blot. The E2F1 was identified as the target of miR-329. Overexpression of miR-329 blocked G1/S transition in LN18 and T98G cell lines, dramatically suppressed cell proliferation and the ability of colony formation. MiR-329 significantly decreased the phosphorylation levels of intracellular kinases Akt and expression of cyclin D1, but the expression of p21 was upregulated, cell growth was suppressed by inhibiting E2F1-mediated Akt pathway. MiR-329 may inhibit cell proliferation in human glioma cells through regulating E2F1-mediated suppression of Akt pathway.


[Changes in the expression of vital cytokines for pancreatic development in early embryo].
To clarify the changes in the expression of vital cytokines for pancreatic development in early embryo and hence provide preclinical data regarding embryonic pancreas transplanted for treatment, of diabetes mellitus. Sample collection was conducted in accordance to the principle of informed consent. Histochemical S-ABC method was adopted in studying pancreas at 7-12 weeks of gestation, and analysis was made on vital cytokines expression as well as the differentiation and forming of pancreatic islets. It was found that the expression of Insulin, Glucagon, Somatostatin and Cytokeratin begins at 7 weeks, and the change is consistent with the differentiation and formation of pancreatic islets. IGF-I and F-VIII appear at 12 weeks. Insulin, Glucagon, Somatostatin, Cytokeratin, IGF-I and F-VIII play a regulatory role in the development of embryonic pancreas and are related to the differentiation and formation of endocrine and exocrine glands of pancreas. The pancreas after 12 weeks of gestation can be used as a donated graft for pancreas transplantation.


Epidemic typhus.
Epidemic typhus is transmitted to human beings by the body louse Pediculus humanus corporis. The disease is still considered a major threat by public-health authorities, despite the efficacy of antibiotics, because poor sanitary conditions are conducive to louse proliferation. Until recently, Rickettsia prowazekii, the causal agent, was thought to be confined to human beings and their body lice. Since 1975, R prowazekii infection in human beings has been related to contact with the flying squirrel Glaucomys volans in the USA. Moreover, Brill-Zinsser disease, a relapsed form of epidemic typhus that appears as sporadic cases many years after the initial infection, is unrelated to louse infestation. Stress or a waning immune system are likely to reactivate this earlier persistent infection, which could be the source of new epidemics when conditions facilitate louse infestation. Finally, R prowazekii is a potential category B bioterrorism agent, because it is stable in dried louse faeces and can be transmitted through aerosols. An increased understanding of the pathogenesis of epidemic typhus may be useful for protection against this bacterial threat.


Rapid breeding of parthenocarpic tomato plants using CRISPR/Cas9.
Parthenocarpy in horticultural crop plants is an important trait with agricultural value for various industrial purposes as well as direct eating quality. Here, we demonstrate a breeding strategy to generate parthenocarpic tomato plants using the CRISPR/Cas9 system. We optimized the CRISPR/Cas9 system to introduce somatic mutations effectively into SlIAA9-a key gene controlling parthenocarpy-with mutation rates of up to 100% in the T0 generation. Furthermore, analysis of off-target mutations using deep sequencing indicated that our customized gRNAs induced no additional mutations in the host genome. Regenerated mutants exhibited morphological changes in leaf shape and seedless fruit-a characteristic of parthenocarpic tomato. And the segregated next generation (T1) also showed a severe phenotype associated with the homozygous mutated genome. The system developed here could be applied to produce parthenocarpic tomato in a wide variety of cultivars, as well as other major horticultural crops, using this precise and rapid breeding technique.


Important differences in clinical data from third, second, and first generation periodontal probes.
This study compared relative attachment levels (RAL) and probable crevice depths (PCD) from 6 periodontal probes (1 third, 4 second, and 1 first generation). A single clinician recorded RAL and PCD in 6 patients with chronic adult periodontitis (mean age 48.2 years) during two visits (interval: 1 week) using a Latin square examination order. Replicate measurements were recorded at the 4 interproximal sites of the Ramford index teeth to examine intra-probe differences. Additional single measurements were recorded at similar sites of units 11, 26, 31 and 46 to investigate interprobe differences. Intra-probe RAL and PCD reproducibility was < or = 1 mm at > 94% of the sites. All intra-probe Pearson correlation coefficients were > 0.85 (P = 0.00). Inter-probe RAL and PCD agreement was < or = 1 mm at > 49% of the sites for RAL and > 61% of the sites for PCD. All inter-probe Pearson correlation coefficients were > 0.42 (P = 0.00) for RAL and > 0.49 (P = 0.00) for PCD. Analyses of variance showed significant differences in RAL and PCD between the first generation probe and the second generation probes (P < 0.005); in RAL between the third generation probe and the first and second generation probes (P = 0.0354); and in PCD between the third generation probe and the first and second generation probes (P = 0.0475). Inter-probe differences were clinically significant in the recorded percentages of pockets > or = 4 mm and > or = 6 mm. Significant inter-probe differences were found in RAL and PCD which have clinical importance in data interpretation and comparison.


Inhibition of cellular adhesion in human umbilical vein endothelial cells by NF-kappaB inhibitor DHMEQ under flow.
We previously designed and synthesized DHMEQ as an inhibitor of NF-kappaB. In the present study, we looked into the effect of DHMEQ on the cell adhesion in human umbilical vein endothelial cells (HUVEC) under flow. We used freshly prepared HUVEC and human mononuclear cells throughout the experiment. DHMEQ inhibited TNF-alpha-, IL-1beta-, and LPS-induced NF-kappaB activation in HUVEC. It also inhibited TNF-alpha-induced expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. DHMEQ also inhibited TNF-alpha-induced mononuclear cell-HUVEC adhesion. The effect of DHMEQ was more prominent when the cells were under shear stress. DHMEQ inhibited the adhesion between HUVEC and HT-29 colon cancer cells more clearly under the flow condition than under the static condition of the culture medium. These results suggest that DHMEQ, being a unique inhibitor of NF-kappaB, may be effective in suppressing atherosclerosis and metastasis by inhibiting the expression of adhesion molecules.


Hyperbaric oxygen treatment attenuates neuropathic pain by elevating autophagy flux via inhibiting mTOR pathway.
Peripheral neuropathic pain is a complex disease, and treated based on underlying diseases. Emerging evidences suggest that hyperbaric oxygen alleviates neuropathic pain. However, its cellular and molecular mechanism on pain relief is unknown. We hypothesize that hyperbaric oxygen alleviates neuropathic pain via activating autophagy flux and inhibiting mTOR pathway. Hyperbaric oxygen effectively inhibited nerve injury induced autophagy impairment and mTOR pathway activation in a rat spinal nerve ligation (SNL) model. Moreover, intrathecal injection of rapamycin, an autophagy inducer, enhanced hyperbaric oxygen effect by further decreasing mTOR activity. In contrast, chloroquine, an autophagy inhibitor, counteracted hyperbaric oxygen analgesic effect. These findings indicate that hyperbaric oxygen attenuated neuropathic pain by increasing spinal autophagic flux via inhibiting mTOR pathway. Our study provides pre-clinical evidences in expediting hyperbaric oxygen become a safe clinical treatment of neuropathic pain.


The relationship of blood glucose with cardiovascular disease is mediated over time by traditional risk factors in type 1 diabetes: the DCCT/EDIC study.
Chronic hyperglycaemia, as measured by HbA1c levels, is a major risk factor for atherosclerosis and cardiovascular disease (CVD) in type 1 diabetes. Our aim was to describe the degree to which the effect of HbA1c on the risk of CVD is mediated by its effect on traditional risk factors over time, and how these mediation pathways change over time. The DCCT and its observational follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC), followed 1441 participants for a mean of 27 years, with periodic measurement of HbA1c and risk factors over time. We assessed the proportion of the HbA1c effect on risk of CVD that was mediated through its effects on systolic BP (SBP), pulse rate, triacylglycerols and LDL-cholesterol (LDLc) levels, and how the proportion mediated changed over time. The association of HbA1c with CVD outcomes was stable over time, while that of traditional risk factors (SBP, pulse rate, triacylglycerols and LDLc) increased. At 10 years of follow-up, the effect of HbA1c on 10 year CVD risk was minimally mediated by SBP (2.7%), increasing to 26% at 20 years. Likewise, from 10 year follow-up to 20 year follow-up, the proportion of HbA1c effect mediated through pulse rate increased from 6.3% to 29.3%, through triacylglycerols from 2.2% to 22.4%, and through LDLc from 9.2% to 30.7%. As participants age, the predictive association of mean HbA1c on subsequent CVD events is increasingly mediated by its effect on standard risk factors. Thus, management of traditional non-glycaemic CVD risk factors may have increasing benefits in an ageing type 1 diabetes population with longstanding hyperglycaemia. ClinicalTrials.gov NCT00360893 and NCT00360815.


Therapeutic salivary monitoring of IV busulfan in patients undergoing hematopoietic stem cell transplantation: a pilot study.
Individual therapeutic monitoring of busulfan (BU) minimizes its toxicity and improves the therapeutic outcomes during hematopoietic stem cell transplantation (HSCT). For individual dose adjustment, several blood collections are performed that are uncomfortable for patients. The aim of this pilot study was to validate a laboratory method for quantification of BU in saliva and to present the results obtained using this protocol in HSCT patients. We performed analyses of selectivity, precision and accuracy of saliva with standard concentrations of BU using ultra-high-performance liquid chromatography with diode array detection. We also determined salivary and plasmatic concentrations of BU in six HSCT patients. Saliva exhibited excellent selectivity, precision and accuracy for quantification of BU. In the patient samples, significant correlations were noted between plasmatic and salivary concentrations of BU (r=0.97, P<0.001 in the test dose; r=0.93, P<0.001 in the adjusted dose). Passing &Bablok regression revealed good agreement between the two methods (R2=0.956 for test dose; R2=0.927 for adjusted dose). In conclusion, the saliva is safe for laboratory BU measurement. The good agreement with plasma encourages further clinical studies using saliva for BU therapeutic monitoring.


Guidelines for detection of breast cancer: an update on investigative methods. A report of the ad hoc committee on mammography of The Canadian Association of Radiologists.
The high incidence of breast cancer and its mortality make it imperative that women over 25 years of age have a clinical examination of their breasts at least every three years up to age 40 and annually thereafter. Before the age of 25, mammography is seldom indicated and then it should usually be limited to a spot film of a potential lesion. After 25, mammography is indicated for any woman with breast symptoms, women with metastases from cancer of an unknown primary site, and before any breast surgery. Women with a strong family history and those with large breasts should also have a mammogram between the ages of 25 and 35. Between the ages of 35 and 39 we recommend a baseline mammogram for asymptomatic women. After 39 and up to age 50, women should consult their physicians yearly to determine if, and how often, mammography should be performed. Finally, after age 50, annual mammography is suggested. In each of the above contexts, the radiologic examination should be coupled with clinical palpation of the breasts. A trained and experienced mammographer should recommend biopsy when mammograms show a typical spiculated mass; an ill-defined or even well defined mass that cannot be said to be benign; a suspicious distortion of local architecture; or a cluster of suspicious microcalcifications. Any cyst the nature of which is uncertain after puncture, or abnormal ducts on a galactogram also should make a biopsy mandatory. On the other hand, a normal mammogram should not prevent biopsy of a lesion of the nipple or of a lump detected clinically.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of personal oral hygiene and subgingival scaling on bleeding interdental gingiva.
The aim of this study was to determine the effects of personal oral hygiene and subgingival scaling on bleeding interdental gingiva. The Eastman Interdental Bleeding Index (EIBI) was used to clinically evaluate interdental gingival status. Forty-seven bleeding interdental sites in 47 patients were divided into three groups. Sites in Group I bled on stimulation with wooden interdental cleaners. Groups II and III initially bled but were converted to nonbleeding with oral hygiene alone or oral hygiene combined with subgingival scaling, respectively. Interdental gingival biopsies were obtained and subjected to morphometric analysis to compare the three groups. The findings from this study indicated that: (A) personal oral hygiene reduced the magnitude and extent of the interdental inflammatory lesion; (B) subgingival scaling plus oral hygiene decreased the interdental inflammatory lesion to a greater extent than oral hygiene alone; (C) significant repair of the interdental lesion occurred within four weeks; and (D) the EIBI was an effective method for monitoring the effects of therapy directed towards resolution of the interdental inflammatory lesion.


Brazilian guidelines for the treatment of outpatients with suspected or confirmed COVID-19. A joint guideline of the Brazilian Association of Emergency Medicine (ABRAMEDE), Brazilian Medical Association (AMB), Brazilian Society of Angiology and Vascular Surgery (SBACV), Brazilian Society of Geriatrics and Gerontology (SBGG), Brazilian Society of Infectious Diseases (SBI), Brazilian Society of Family and Community Medicine (SBFMC), and Brazilian Thoracic Society (SBPT).
Several therapies have been used or proposed for the treatment of COVID-19, although their effectiveness and safety have not been properly evaluated. The purpose of this document is to provide recommendations to support decisions about the drug treatment of outpatients with COVID-19 in Brazil. A panel consisting of experts from different clinical fields, representatives of the Brazilian Ministry of Health, and methodologists (37 members in total) was responsible for preparing these guidelines. A rapid guideline development method was used, based on the adoption and/or adaptation of recommendations from existing international guidelines combined with additional structured searches for primary studies and new recommendations whenever necessary (GRADE-ADOLOPMENT). The rating of quality of evidence and the drafting of recommendations followed the GRADE method. Ten technologies were evaluated, and 10 recommendations were prepared. Recommendations were made against the use of anticoagulants, azithromycin, budesonide, colchicine, corticosteroids, hydroxychloroquine/chloroquine alone or combined with azithromycin, ivermectin, nitazoxanide, and convalescent plasma. It was not possible to make a recommendation regarding the use of monoclonal antibodies in outpatients, as their benefit is uncertain and their cost is high, with limitations of availability and implementation. To date, few therapies have demonstrated effectiveness in the treatment of outpatients with COVID-19. Recommendations are restricted to what should not be used, in order to provide the best treatment according to the principles of evidence-based medicine and to promote resource savings by aboiding ineffective treatments.


Integrating Welfare Technology in Long-term Care Services: Nationwide Cross-sectional Survey Study.
Welfare technologies are often described as a solution to the increasing pressure on primary health care services. However, despite initiating welfare technology projects in the health care sector and different government incentives, research indicates that it is difficult to integrate welfare technology innovations in a complex and varying setting, such as long-term care. We aim to describe the types of welfare technology and the extent to which welfare technology is provided in long-term care (ie, nursing homes and home care services); examine whether the extent of welfare technology provision differs on the basis of municipal characteristics (ie, population size, centrality, the proportion of older inhabitants, and income); and identify how local governments (ie, municipalities) describe their efforts toward integrating welfare technologies in long-term care. Quantitative and qualitative data about welfare technology from a larger cross-sectional survey about the provision of long-term care services in Norwegian municipalities were combined with registry data. Representatives of 422 Norwegian municipalities were invited to participate in the survey. Frequencies were used to describe the distribution of the types and extent of welfare technologies, whereas the Fisher exact test and Kruskal-Wallis one-way analysis of variance were used to determine the association between the extent of welfare technology and municipal characteristics. Free-form text data were analyzed using thematic analysis. A total of 277 municipalities were surveyed. Technology for safety was the most widespread type of welfare technology, whereas technology for social contact was the least prevalent. Two-thirds of the sample (183/277, 66.1%) in nursing home and (197/277, 71.1%) in home care services reported providing one or two different types of welfare technology. There was a statistically significant association between the extent of welfare technology and population size (in both nursing homes and home care services: P=.01), centrality (nursing homes: P=.01; home care services: P<.001), and municipal income (nursing homes: P=.02; home care services: P<.001). The extent of welfare technology was not associated with the proportion of older adults. The municipalities described being in a piloting phase and committing to future investment in welfare technology. Monetary resources were allocated, competency development among staff was initiated, and the municipalities were concerned about establishing collaborations within and between municipalities. Home care services seem to have a more person-centered approach in their efforts toward integrating welfare technologies, whereas nursing homes seem to have a more technology-centered approach. Many municipalities provide welfare technologies; however, their extent is limited and varies according to municipal characteristics. Municipal practices still seem dominated by piloting, and welfare technologies are not fully integrated into long-term care services. Innovation with welfare technology appears top-down and is influenced by national policy but also reflects creating a window of opportunity through the organization of municipal efforts toward integrating welfare technology through, for example, collaborations and committing personnel and financial resources.


Immortalization of human keratinocytes by simian virus 40 large T-antigen alters keratin gene response to retinoids.
Immortalized, but nontumorigenic, human keratinocyte cell lines have many potential therapeutic and experimental uses. We have utilized a recombinant retrovirus, encoding the simian virus 40 large T-antigen, to immortalize normal human epidermal keratinocytes. The KER-1 cells derived from the immortalization process grow without feeder layer support, but do not form colonies in soft agar. Morphologically, the KER-1 cells appear similar to nonimmortalized cells, except that stratification is somewhat reduced. The pattern of keratin gene expression in nonimmortalized and KER-1 cells is similar, except for the retinoid-dependent regulation of type I cytokeratin, K7, in the KER-1 cells. This keratin is not expressed in nonimmortalized keratinocytes, but is present at low levels in KER-1 cells. Incubation with trans-retinoic acid (20 or 200 nM) or retinol (200 or 2000 nM) results in a 40-fold increase in K7 expression in KER-1 cells. The cornified envelope precursor, involucrin, is expressed at normal levels in KER-1 cells. Moreover, as in nonimmortalized cells, KER-1 involucrin levels are not suppressed by retinoids. trans-Retinoic acid and retinol reduce envelope formation in both nonimmortalized keratinocytes and KER-1 cells. Surprisingly, the synthetic retinoid, Ro 13-6298 (p [(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- naphthyl)-propenyl]benzoic acid ethyl ester), a potent regulator of keratin gene expression, cornified envelope formation and morphological change in nonimmortalized cells, is completely inactive in KER-1 cells.


Successful removal of permanent spinal cord stimulators in patients with complex regional pain syndrome after complete relief of pain.
It is uncommon for patients who have received a permanent implant to remove the spinal cord stimulator (SCS) after discontinuation of medication in complex regional pain syndrome (CRPS) due to their completely painless state. This study evaluated CRPS patients who successfully removed their SCSs. This 10-year retrospective study was performed on patients who had received the permanent implantation of an SCS and had removed it 6 months after discontinuation of stimulation, while halting all medications for neuropathic pain. Age, sex, duration of implantation, site and type of CRPS, and their return to work were compared between the removal and non-removal groups. Five (12.5%, M/F = 4/1) of 40 patients (M/F = 33/7) successfully removed the permanent implant. The mean age was younger in the removal group (27.2 ± 6.4 vs. 43.5 ± 10.7 years, P < 0.01). The mean duration of implantation in the removal group was 34.4 ± 18.2 months. Two of 15 patients (13.3%) and 3 of 25 patients (12%) who had upper and lower extremity pain, respectively, had removed the implant. The implants could be removed in 5 of 27 patients (18.5%) with CRPS type 1 (P < 0.01). All 5 patients (100%) who removed their SCS returned to work, while only 5 of 35 (14.3%) in the non-removal group did (P < 0.01). Even though this study had limited data, younger patients with CRPS type 1 could remove their SCSs within a 5-year period and return to work with complete pain relief.


Human antibodies neutralize enterovirus D68 and protect against infection and paralytic disease.
Enterovirus D68 (EV-D68) causes outbreaks of respiratory illness, and there is increasing evidence that it causes outbreaks of acute flaccid myelitis (AFM). There are no licensed therapies to prevent or treat EV-D68 infection or AFM disease. We isolated a panel of EV-D68-reactive human monoclonal antibodies that recognize diverse antigenic variants from participants with prior infection. One potently neutralizing cross-reactive antibody, EV68-228, protected mice from respiratory and neurologic disease when given either before or after infection. Cryo-electron microscopy studies revealed that EV68-228 and another potently neutralizing antibody (EV68-159) bound around the fivefold or threefold axes of symmetry on virion particles, respectively. The structures suggest diverse mechanisms of action by these antibodies. The high potency and effectiveness observed in vivo suggest that antibodies are a mechanistic correlate of protection against AFM disease and are candidates for clinical use in humans with EV-D68 infection.


Homocysteine Levels in Severe OSA Patients Before and After TORS-OSA Surgery.
The increased risk of cardiovascular diseases owing to a high level of serum homocysteine has been widely reported. Literature has demonstrated that patients with obstructive sleep apnea/hypopnea syndrome (OSA) had a higher homocysteine level than control group. This study aimed to investigate the alteration of serum homocysteine levels in severe OSA patients receiving transoral robotic surgery (TORS). Retrospective chart review. Tertiary academic medical center. Data of polysomnography (PSG) and serum homocysteine levels before and at least 3 months after the surgery were collected and analyzed via paired t tests. A subgroup analysis based on the preoperative homocysteine level (≥15 mcmol/L, as hyperhomocysteinemia group) was conducted to compare the intergroup differences of homocysteine decrease. Pearson's correlation was used to survey the relationships between the changes of major PSG parameters and the levels of homocysteine decrease at baseline and after TORS-OSA surgery. Two hundred sixty-one patients with severe OSA were enrolled. There were significant improvements in major PSG parameters after TORS-OSA surgery. Homocysteine levels significantly decreased from 12.1 ± 3.9 to 11.4 ± 3.7 mcmol/L (difference = -0.7 ± 2.8 mcmol/L, p = .001) postoperatively, which was shown in the hyperhomocysteinemia group (difference = -2.9 ± 4.7 mcmol/L, p = .007) to a greater extent. Pearson's correlation revealed that ΔODI (oxygen desaturation index/h) was the predominant estimate with a positive association with Δhomocysteine (r = 0.525, p = .012). TORS-OSA surgery could decrease homocysteine levels in OSA patients. The effects were more relevant in severe OSA patients with abnormal preoperative homocysteine levels.


Upconversion luminescence properties of Yb3+, Gd3+, and Tm3+ co-doped NaYF4 microcrystals synthesized by the hydrothermal method.
Yb3+/Gd3+/Tm3+ co-doped prism-like NaYF4 microcrystals were synthesized through a facile ethylene diamine triacetic acid (EDTA)-assisted hydrothermal method. The microcrystals were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), upconversion (UC) emission spectra, and decay curve. After annealing in an argon atmosphere, the microcrystals emitted bright blue and intense ultraviolet (UV) light under a 980-nm continuous wave diode laser excitation. Besides the UC emissions of the Tm3+ ions, 6D(J), 6I(J) and 6P(J) --> 8S7/2 UC emissions of Gd3+ were observed. During the emission process of Gd3+ ions, both Yb3+ and Tm3+ ions served as sensitizers. In the complex excitation and frequency UC processes, excited state absorption of Gd3+ ions, cross relaxation energy transfer (CRET) between two excited Gd3+ ions, and energy transfer (ET) between Gd3+ and Yb3+ or Tm3+ ions played key roles for the UC emissions of Gd3+ ions.


Primary urachal leiomyosarcoma: a case report and literature review of clinical, pathological, and medical imaging features.
Urachal tumors are exceedingly rare, and adenocarcinoma is the most common malignant urachal neoplasm. Here, an especially rare patient of primary urachal leiomyosarcoma from our hospital was reported, and only five patients have been reported thus far since 1981. A 24-year-old man was admitted due to urinary tract symptoms. Both urogenital ultrasonography and contrast-enhanced computed tomography showed a mass at the dome of the urinary bladder. Laparoscopic surgical resection was performed, and histopathologic examination of the mass confirmed the diagnosis of urachal leiomyosarcoma. No recurrence was noted after one and a half years. Because the leiomyosarcoma located in the extraperitoneal space of Retzius and may manifest with nonspecific abdominal or urinary symptoms, early and definitive preoperative diagnosis is challenging. Partial cystectomy with complete excision of the urachus is recommended. Because only a few patients have been recorded, clinical outcomes and recurrence risks are difficult to assess.


[A meta-analysis of perioperative hyperoxia for the surgical site infections in patients with general surgery].
To systemically analyze the effect of perioperative hyperoxia for the surgical site infections in patients with general surgery. Electronic databases consisting of Pubmed, Embase, Cochrane Library, Wanfang Database, CNKI and VIP were systemically searched from established time to November 18, 2015. The randomized controlled trials about perioperative high and low-concentration oxygen for the surgical site infections in patients with general surgery were screened strictly and analyzed by the software of Revman 5.3. The included trials were stratified according to the colorectal or non-colorectal surgery, the duration of oxygen inhalation and the kinds of mixed gas to perform subgroup analyses. Sensitivity analysis was conducted by removing the low-quality trials, etc. The outcome was the surgical site infections. There were 989 relevant articles were searched out. At last, 9 randomized controlled trials consisting of 3 281 patients were included. The 80% oxygen group and 30% oxygen group consists of 1 644 and 1 637 patients, respectively. The rates of surgical site infection were 15.1% (248/1 644) and 17.5% (286/1 637) in the two group. Heterogeneity existed between the included trials and random-effect model was used, the RR=0.80, 95%CI: 0.60-1.08, P=0.15. Therefore, statistically significant difference was not found for the surgical site infections in the general surgery between the perioperative high and low-concentration oxygen. However, the results of subgroup analyses showed that the perioperative hyperoxia decreaced the surgical site infections significant in the subgroups of colorectal surgery and intraoperative plus postoperative 6 h oxygen inhalation. Perioperative hyperoxia does not reduce surgical site infections in patients with general surgery. However, the results of two subgroup analyses (colorectal surgery and intraoperative plus postoperative 6 h oxygen inhalation trials) show a significantly benefit for perioperative hyperoxia in decreasing surgical site infections.


A FTIR and DFT Combination Study to Reveal the Mechanism of Eliminating the Azeotropy in Ethyl Propionate-n-Propanol System with Ionic Liquid Entrainer.
Ionic liquids (ILs) have presented excellent behaviors in the separation of azeotropes in extractive distillation. However, the intrinsic molecular nature of ILs in the separation of azeotropic systems is not clear. In this paper, Fourier-transform infrared spectroscopy (FTIR) and theoretical calculations were applied to screen the microstructures of ethyl propionate-n-propanol-1-ethyl-3-methylimidzolium acetate ([EMIM][OAC]) systems before and after azeotropy breaking. A detailed vibrational analysis was carried out on the v(C=O) region of ethyl propionate and v(O-D) region of n-propanol-d1. Different species, including multiple sizes of propanol and ethyl propionate self-aggregators, ethyl propionate-n-propanol interaction complexes, and different IL-n-propanol interaction complexes, were identified using excess spectroscopy and confirmed with theoretical calculations. Their changes in relative amounts were also observed. The hydrogen bond between n-propanol and ethyl propionate/[EMIM][OAC] was detected, and the interaction properties were also revealed. Overall, the intrinsic molecular nature of the azeotropy breaking was clear. First, the interactions between [EMIM][OAC] and n-propanol were stronger than those between [EMIM][OAC] and ethyl propionate, which influenced the relative volatilities of the two components in the system. Second, the interactions between n-propanol and [EMIM][OAC] were stronger than those between n-propanol and ethyl propionate. Hence, adding [EMIM][OAC] could break apart the ethyl propionate-n-propanol complex (causing the azeotropy in the studied system). When x([EMIM][OAC]) was lower than 0.04, the azeotropy still existed mainly because the low IL could not destroy the whole ethyl propionate-n-propanol interaction complex. At x(IL) > 0.04, the whole ethyl propionate-n-propanol complex was destroyed, and the azeotropy disappeared.