Glucocorticoid replacement in pituitary surgery: guidelines for perioperative assessment and management.
Patients undergoing surgical resection of pituitary adenomas are frequently given perioperative glucocorticoid therapy. There are no randomized controlled studies assessing the need for such steroids; however, several studies have documented changes in the hypothalamic-pituitary-adrenal (HPA) axis associated with pituitary surgery. Based on the evidence available, this article details recommendations for the perioperative management of glucocorticoid therapy in patients with pituitary tumors. For patients with proven ACTH deficiency preoperatively [usually based on response to a short ACTH 1-24 (Synacthen) test], 48 hours of supraphysiological glucocorticoid therapy should be administered perioperatively (e.g. hydrocortisone, 50 mg every 8 hours on day 0, 25 mg every 8 hours on day 1, and 25 mg at 0800 h on day 2). For patients with intact HPA function preoperatively, and in whom selective adenomectomy is possible, perioperative glucocorticoids are not necessary. Early postoperative assessment depends on daily clinical assessment of the patient and 0800 h plasma cortisol levels. Cortisol levels over 450 nM (16 microg/dl) reflect normal HPA function, and levels less than 100 nM (3.6 microg/dl) are consistent with ACTH deficiency. Cortisol levels between 100 and 250 nM (3.6-9 microg/dl) may be ACTH deficient and should receive morning hydrocortisone replacement until definitive HPA axis testing. Cortisol levels between 250 and 450 nM (9-16 microg/dl) are unlikely to be ACTH deficient but should receive additional steroids for stress until a definitive test is performed. For those requiring definitive testing, the insulin tolerance test, the overnight metyrapone test, or the glucagon stimulation test are appropriate and may be performed as early as d 7-10 or, if more convenient, wk 4-6. Following the guidelines suggested here should reduce the use of unnecessary glucocorticoids, while ensuring the safety of patients is not compromised.


Efficient Direct Reduction of Graphene Oxide by Silicon Substrate.
Graphene has been studied for various applications due to its excellent properties. Graphene film fabrication from solutions of graphene oxide (GO) have attracted considerable attention because these procedures are suitable for mass production. GO, however, is an insulator, and therefore a reduction process is required to make the GO film conductive. These reduction procedures require chemical reducing agents or high temperature annealing. Herein, we report a novel direct and simple reduction procedure of GO by silicon, which is the most widely used material in the electronics industry. In this study, we also used silicon nanosheets (SiNSs) as reducing agents for GO. The reducing effect of silicon was confirmed by various characterization methods. Furthermore, the silicon wafer was also used as a reducing template to create a reduced GO (rGO) film on a silicon substrate. By this process, a pure rGO film can be formed without the impurities that normally come from chemical reducing agents. This is an easy and environmentally friendly method to prepare large scale graphene films on Si substrates.


HRV Monitoring Using Commercial Wearable Devices as a Health Indicator for Older Persons during the Pandemic.
Remote monitoring platforms based on advanced health sensors have the potential to become important tools during the COVID-19 pandemic, supporting the reduction in risks for affected populations such as the elderly. Current commercially available wearable devices still have limitations to deal with heart rate variability (HRV), an important health indicator of human aging. This study analyzes the role of a remote monitoring system designed to support health services to older people during the complete course of the COVID-19 pandemic in Brazil, since its beginning in Brazil in March 2020 until November 2021, based on HRV. Using different levels of analysis and data, we validated HRV parameters by comparing them with reference sensors and tools in HRV measurements. We compared the results obtained for the cardiac modulation data in time domain using samples of 10 elderly people's HRV data from Fitbit Inspire HR with the results provided by Kubios for the same population using a cardiac belt, with the data divided into train and test, where 75% of the data were used for training the models, with the remaining 25% as a test set for evaluating the final performance of the models. The results show that there is very little difference between the results obtained by the remote monitoring system compared with Kubios, indicating that the data obtained from these devices might provide accurate results in evaluating HRV in comparison with gold standard devices. We conclude that the application of the methods and techniques used and reported in this study are useful for the creation and validation of HRV indicators in time series obtained by means of wearable devices based on photoplethysmography sensors; therefore, they can be incorporated into remote monitoring processes as seen during the pandemic.


Description of a new Cladolasma (Opiliones: Nemastomatidae: Ortholasmatinae) species from China.
The harvestmen genus Cladolasma Suzuki, 1963, previously known only from Japan and Thailand, is here reported from China for the first time. A new species, Cladolasma damingshan sp. nov., is described on the basis of a single male specimen collected from Daming Mountain, Guangxi, China. The new species is distinct from C. parvulum Suzuki, 1963 and C. angka (Schwendinger & Gruber, 1992) in lacking keels around the eyes; and from the known males of C. parvulum in the arrangement of large spines on the penial glans. The finding also represents the first record of Nemastomatidae and Ortholasmatinae for China.


Benefits associated with achieving optimal risk factor levels for the primary prevention of cardiovascular disease in older men.
Most incident cardiovascular disease (CVD) occurs after patients reach the age of 65. The additive benefits of aggressive risk factor management with advancing age are not well established. To evaluate the relationship between control of four modifiable risk factors (smoking, non-high density lipoprotein cholesterol, blood pressure, and aspirin use) and risk of CVD in a primary prevention population of older men. U.S. male physicians from the Physicians' Health Study (n = 4182; an epidemiologic follow-up of a randomized trial of aspirin and beta-carotene) who in 1997 were ≥ 65 years, free of CVD and diabetes, and had a blood sample on file were studied. Cox proportional hazard models were adjusted for age and competing causes of death. The first of any CVD event, defined as cardiovascular death, nonfatal myocardial infarction, angina, coronary revascularization, nonfatal stroke, transient ischemic attack, carotid artery surgery, and other peripheral vascular disease surgery, was measured. Mean follow-up was 9.3 years, mean age was 73 years, and 96% were nonsmokers. Compared with when 4 of 4 risk factors were controlled (6.0% of participants), control of 0 of 4 risk factors almost quadrupled the risk of CVD (0.4% of participants; event rate 41.2%; hazard ratio [HR] 3.83, 95% confidence interval [95% CI] 1.72-8.55); control of 1 of 4 risk factors more than doubled the risk (14.2% of participants; HR 2.53, 95% CI 1.80-3.57); control of 2 of 4 risk factors almost doubled the risk (43.8% of participants; HR 1.94, 95% CI 1.41-2.69), and those with control of 3 of 4 risk factors also were at increased risk (35.6% of participants; HR 1.80, 95% CI 1.30-2.50). Control of each additional risk factor was associated with greater cardiovascular protection (P for trend P = .002). Depending on the number of risk factors controlled, the number-needed to control to prevent one CVD event ranged from 5 to 22. Control of 4 treatable risk factors (nonsmoking, control of non-high density lipoprotein cholesterol and blood pressure, and aspirin use) was associated with substantial protection against incident cardiovascular events in older men even after adjustment for competing causes of mortality.


Effects of chelidonic acid, a secondary plant metabolite, on mast cell degranulation and adaptive immunity in rats.
The present study evaluated the immunomodulatory effects of chelidonic acid, a secondary plant metabolite, with therapeutic potential in allergic disorders, in experimental animals. In mast cell degranulation studies, ovalbumin immunized and challenged rats, chelidonic acid (1, 3 and 10mg/kg, i.p.) dose relatedly prevented ovalbumin challenge induced mast cell degranulation by differing degrees when compared with vehicle treated group, and these effects were comparable with prednisolone (10mg/kg). A reduction in post-challenge mortality was also observed in all treated groups. Further, there were reductions in the blood eosinophil counts and serum IgE levels after chelidonic acid treatment. Chelidonic acid also inhibited histamine release from rat peritoneal mast cells (RPMC) in vitro, in a dose related manner. In tests for adaptive immunity, in rats immunized with sheep RBC, chelidonic acid differentially suppressed the (a) plaque forming cell (PFC) count in rat splenic cells, (b) anti-SRBC antibody titre and serum IgG levels and (c) increases in foot pad thickness in the DTH assay - all of which were comparable with prednisolone. These experimental results are discussed in light of the possible therapeutic potential of chelidonic acid in allergic disorders.


A simple digital filter to remove line-frequency noise in implantable pulse generators.
This study investigated computer simulations and animal studies of a simple digital notch filter to remove 50-and 60-Hz line-frequency-noise interference. The digital notch filter was achieved by computing running subtraction of the intracardiac electrogram and the electrogram recorded one notch-sample period previously. Simultaneous rejection of the two worldwide line frequencies was obtained by computation of the minimum of two separate notch-filter outputs. Power consumption of this numerical algorithm was reduced for applications in implantable devices by operating the notch filters only from 20 msec to 50 msec after a sense event. A sense event was classified as a noise sense if the sum of notch-filter output during this window was less than a preset threshold of the sum of the raw data during the same time window. Otherwise, the sense event was classified as a true sense. The computer simulations determined an optimum threshold value of 33%. The filter was tested in five animal studies using a signal generator to inject additive noise interference. The results indicated that this simple filter could be implemented in an implantable pulse generator and could effectively exclude incorrect line-frequency-noise senses at the notched frequencies.


Neurobiological processes in alcohol addiction.
This article represents the proceedings of a symposium at the ISBRA Meeting in Yokohama, Japan. The chairs were A. D. Lê and K. Kiianmaa. The presentations were (1) Alcohol reward and aversion, by C. L. Cunningham; (2) The role of sensitization of neuronal mechanisms in ethanol self-administration, by J. A. Engel, M. Ericson, and B. Söderpalm; (3) Alcohol self-administration in dependent animals: Neurobiological mechanisms, by G. F. Koob, A. J. Roberts, and F. Weiss; (4) Stress and relapse to alcohol, by A. D. Lê; (5) Alcohol-preferring AA and alcohol-avoiding ANA rats differ in locomotor activation induced by repeated morphine injections, by P. Hyytiä, S. Janhunen, J. Mikkola, P. Bäckström, and K. Kiianmaa; and (6) Initial sensitivity and acute functional tolerance to the hypnotic effects of ethanol in mice genetically selected for mild and severe ethanol withdrawal convulsions, by I. Ponomarev and J. C. Crabbe.


Cytophagocytosis by the blast cells in acute myeloid leukemia.
The occurrence of cytophagocytosis as spontaneous ingestion of cells by blast cells has been poorly investigated in acute leukemia. Cytophagocytosis by blasts in acute myeloid leukemia (AML) was observed in eleven patients who represent 1% of AML cases seen in our institution (one M1, two M2, four M4 and four M5). Prominent features of cytophagocytosis by AML blasts are particularly evident in leukemias involving monocytic cells and were more obvious in the bone marrow than the peripheral blood. AML of the monocytic type with cytophagocytosis are frequently associated with cytogenetic aberrations involving chromosomes 8 and 16. Finally the poor outcome of AML patients with cytophagocytosis and their poor response to therapy and short survival is stressed.


External Evaluation of Four Hospitals According to Patient-centred Care Standards.
Hospital accreditation is a multi-factorial issue. The aim of the current study was to accredit social security organization and university hospitals (that certificated by ISO 9001-2008) in Isfahan, the second largest city of Iran, based on Joint Commission International (JCI) accreditation standards. Accreditation of four hospitals was evaluated and compared in a cross-sectional study. Seven checklists were driven from patient-centered JCI accreditation standards to cover indices of access of patients to care and continuity of care (ACC), patients and families rights (PFR), patients and families education (PFE), assessment of patients (AOP), care of patients (COP), analgesic and surgical care (ASC), and medication management and use (MMU). They were filled out by seven inspectors. The findings were analyzed by SPSS 14 (SPSS Inc., Chicago, IL). Beheshti and Zahra hospitals demonstrated the lowest and the highest mean levels preparation, respectively (60 vs. 68.5 percent, respectively). Also, Beheshti hospital revealed the lowest prepared levels in AOP, ASC, MMU and PFE among all evaluated hospitals; the corresponding mean amounts of preparation were 68, 82.5, 56 and 42 percent, respectively. Whereas Zahra hospital showed the highest prepared levels in AOP, COP, MMU and PFE among all evaluated hospitals; the mean amounts of preparation were 82, 61.5, 84 and 57 percent, respectively. No significant difference was found among the four hospitals in any of the seven indices. The four evaluated hospitals were not fully prepared to present the best possible patient-centered care system.


An illumination of the ICN's core competencies in disaster nursing version 2.0: Advanced nursing response to COVID-19 outbreak in China.
This study aims to report on the actions and incident management of the advanced practice nurses of a disaster operation team who were deployed in response to the COVID-19 outbreak, and to explore how it illustrated the Core Competencies in Disaster Nursing Version 2.0 delineated by the International Council of Nurses in 2019. This is a descriptive study. The participants (responders) communicated and reported their actions in the operation with headquarter on a popular social media platform in China (WeChat), established specifically for the three-rescue teams. The response approach of advanced nurses to COVID-19 encompassed six of the eight domains of the competencies outlined in ICN CCDN V2.0, namely on preparation and planning, communication, incident management systems, safety and security, assessment and intervention. The response teams of advanced practice nurses in this study clearly demonstrated their competencies in disaster rescue, which fulfilled most of the core competencies set forth by the ICN. The findings of this study contributed to understand the roles played by advanced practice nurses and nurse managers in disaster management and how these relate to the competencies set forth by the ICN.


The role of NO synthases in arginine-dependent small intestinal and colonic carcinogenesis.
Arginine is catabolized by NOS2 and other nitric oxide synthases to form nitric oxide. We evaluated the roles of dietary arginine and Nos2 in Apc-dependent intestinal tumorigenesis in Min mice with and without a functional Nos2 gene. NOS2 protein was expressed only in intestinal tissues of Apc(Min/+) Nos2+/+ mice. NOS3 expression was higher in intestinal tissues of mice lacking Nos2, mainly in the small intestine. When diet was supplemented with arginine (0.2% and 2% in drinking water), lack of Nos2 results in decreased tumorigenesis in both small intestine and colon. In Nos2 knockout mice, supplemental arginine (up to 2%) caused a decrease in small intestinal tumor number and size. The arginine-dependent decrease was associated with an increase in nitrotyrosine formation and apoptosis in the region of intestinal stem cells. Mice expressing Nos2 did not show these changes. These mice did, however, show an arginine-dependent increase in colon tumor number and incidence, while no effect on apoptosis was seen. These changes were associated with increased nitrotyrosine formation in epithelial cells. Mice lacking Nos2 did not show changes in tumorigenesis or nitrotyrosine formation, while demonstrating an arginine-dependent increase in apoptosis. These data suggest that Nos2 and dietary arginine have significant effects on intestinal and colonic tumorigenesis in Min mice. In both tissues, loss of Nos2 is associated with decreased tumorigenesis when mice are supplemented with dietary arginine. In the small intestine, Nos2 prevents the arginine-induced decrease in tumor number and size, which is associated with NOS3 expression and increased apoptosis. In the colon, Nos2 is required for the arginine-induced increase in tumor number and incidence.


Analysis of Selected Risk Factors Depending on the Type of Cerebral Palsy.
Background: Cerebral palsy (CP) is not a defined, separate disease classification, but a set of etiologically diverse symptoms that change with the child's age. According to the up-to-date definition, CP is a group of permanent but not unchanging disorders of movement and/or posture and motor function, which are due to a nonprogressive interference, lesion, or abnormality of the developing/immature brain. CP is one of the most frequent causes of motor disability in children. The aim of the present study was to analyze whether selected risk factors may vary depending on particular types of CP. Methods: 181 children with CP (aged 4-17 years), hospitalized at the Department of Pediatrics and Developmental Age Neurology in Katowice in the years 2008-2016 were retrospectively analyzed in the present study. The assumed risk factors of CP were divided into two groups: 1-pre-conception and prenatal (mother's age, family history of epilepsy, burdened obstetric history, mother's systemic diseases, pregnancy order, multiple pregnancy, duration of pregnancy, bleedings from the genital tract during gestation, arterial hypertension during pregnancy, infections during pregnancy, preterm contractions, maintained pregnancy, premature rupture of membranes, abruptio placentae, and others), 2-perinatal and postnatal (mode of delivery, birth weight, Apgar score at the first and fifth minute, neonatal convulsions, respiratory failure, infections in neonatal and infant period, and intraventricular bleeding). The division into particular CP types was based on Ingram's classification. Results: The following risk factors were the most frequent in the total group: respiratory failure, infections, intraventricular bleeding, and prematurity. Among the analyzed preconception and prenatal factors, the duration of pregnancy and preterm contractions during pregnancy significantly differentiated the subgroups of patients depending on the type of CP. The prevalence of almost all analyzed perinatal, neonatal, and infant-related risk factors (i.e., birth weight, Apgar score at the first and fifth minute, neonatal convulsions, respiratory failure, infections in neonatal and infant period, and intraventricular bleeding) significantly differed between CP types, apart from the mode of delivery. However, in multivariate regression, only intraventricular bleeding was an independent predictor for tetraplegic CP type when compared to joined extrapyramidal and ataxic types (OR = 2.801, p = 0.028). Conclusions: As CP is a syndrome of multifactorial etiology, the identification of CP risk factors entails the need for careful observation and comprehensive care of children in the risk group. The presence of certain risk factors may be a prognostic indicator for particular types of CP. The knowledge about the association between the risk factor(s) and the CP type could be a very useful tool for pediatricians looking after the child at risk of developmental disorders.


Ru-catalyzed decarboxylative cyclization of mandelic acids with acrylates: facile access to the phthalide skeleton.
A new protocol for Ru-catalyzed decarboxylative cyclization of mandelic acids with acrylates was established, which allows efficient construction of the phthalide skeleton. Interestingly, this reaction underwent a decarboxylative process, in which only divinylation was observed, and the subsequent cyclization led to the formation of phthalides.


Update on Contact Lens Treatment of Keratoconus
Keratoconus (KC) is a progressive disease that leads to a decrease in visual acuity and quality and impairs vision-related quality of life. Contact lens (CL) application has a primary place and importance in the correction of the optic problems due to the disease. The corneal changes and increased irregular astigmatism that occur with KC progression necessitate special CL designs and fitting methods. In addition to disease stage, the patient's lens tolerance also plays a role in the application of CLs in KC patients. With recent advances in materials and design technology, the CLs used in the treatment of KC have developed considerably and there are various types available. In this review, we discuss the wide range of CLs, including rigid and soft lenses, hybrid and scleral lenses, and even custom lens designs, in light of recent scientific advances.


Overprescribing of Topical Ocular Corticosteroids and Antibiotics in Out-of-Hours Primary Care in Belgium.
Prescribing patterns by primary care physicians concerning ophthalmic problems were studied using the iCAREdata, a database containing information from the out-of-hours care setting in the Flanders region of Belgium. A very high percentage of prescribed ophthalmic medication was topical antibiotics (89.4%) with tobramycin as the most prevalent substance and in clear conflict with the prevailing guidelines. In addition, a very substantial fraction of prescribed medication contained corticosteroids (30.4%). This is a potentially unsafe option within the technical infrastructure of this setting, which limits the diagnostic possibilities concerning viral infections or preexisting glaucoma risk. We conclude that more efforts are required to limit unnecessary and inappropriate prescribing behavior to further promote patient safety.


Metallurgical Characterization of Welded Joint of Nanostructured Bainite: Regeneration Technique versus Post Welding Heat Treatment.
One of the main limitations in application of nanostructured carbide-free bainite as a construction material is the difficulty of joining. This research presents a structural characterization of welded joints of medium carbon 55Si7 grade steel after the welding process with a regeneration technique as well as post welding heat treatment (PWHT). The hardness distribution of the welded joint with regeneration exhibit an overall decrease in hardness when compared to the base material and a significant decrease in hardness was observed in the heat-affected zone (HAZ). Unfavorable hardness distribution was caused by the presence of diffusion-type transformations products (pearlite) in the HAZ and bainite degradation processes. On the other hand, welding with the PWHT promotes the achievement of a comparable level of hardness and structure as in the base material. However, a slight decrease in hardness was observed in the weld zone due to the micro-segregation of the chemical composition caused by the indissoluble solidification structure. Based on the structural analysis, it was found that steel with relatively low hardenability (55Si7) should be welded using PWHT rather than a regeneration technique.


Selective nanomolar detection of dopamine using a boron-doped diamond electrode modified with an electropolymerized sulfobutylether-beta-cyclodextrin-doped poly(N-acetyltyramine) and polypyrrole composite film.
N-acetyltyramine was synthesized and electropolymerized together with a negatively charged sulfobutylether-beta-cyclodextrin on a boron-doped diamond (BDD) electrode followed by the electropolymerization of pyrrole to form a stable and permselective film for selective dopamine detection. The selectivity and sensitivity of the formed layer-by-layer film was governed by the sequence of deposition and the applied potential. Raman results showed a decrease in the peak intensity at 1329 cm(-1) (sp(3)), the main feature of BDD, upon each electrodeposition step. Such a decrease was correlated well with the change of the charge-transfer resistance derived from impedance data, i.e., reflecting the formation of the layer-by-layer film. The polycrystalline BDD surface became more even with lower surface roughness as revealed by scanning electron and atomic force microscopy. The modified BDD electrode exhibited rapid response to dopamine within 1.5-2 s and a low detection limit of 4-5 nM with excellent reproducibility. Electroactive interferences caused by 4-dihydroxyphenylalanine, 3,4-dihydroxyphenylacetic acid, ascorbic acid, and uric acid were completely eliminated, whereas the signal response of epinephrine and norepinephrine was significantly suppressed by the permselective film.


Immunological and biochemical characterization of the nonspecific cross-reacting antigen epitopes using twenty-three monoclonal antibodies.
Twenty-three monoclonal antibodies (MAbs) reactive with nonspecific cross-reacting antigen (NCA) were prepared and used for constructing a serological map of the NCA molecule. The MAbs were generated using purified NCA or carcinoembryonic antigen (CEA) as immunogen. The MAbs could be divided into two groups: Group X, 10 clones reactive with NCA and CEA; and Group Y, 13 clones specific for NCA. Cross-competition enzyme immunoassays between MAbs of the individual groups revealed that at least 8 different subgroups can be defined i.e., 5 and 3 subgroups in Groups X and Y, respectively. The chemical nature of the epitopes recognized by those MAbs was tested using chemically or enzymatically treated antigens; all MAbs reacted with periodate-treated NCA and deglycosylated NCA, indicating that all the epitopes identified appeared to be protein in nature. Reduction and alkylation, pepsin digestion or pronase treatment of NCA, however, gave some differential results with respect to MAb binding. The serologic mapping and biochemical studies reported here thus provide information as to the range and nature of the epitopes on the NCA molecule and help form the basis for selecting the anti-NCA MAbs for use in biological and immunological study of NCA.


Deep Learning Driven GC-MS Library Search and Its Application for Metabolomics.
Preliminary compound identification and peak annotation in gas chromatography-mass spectrometry is usually made using mass spectral databases. There are a few algorithms that enable performing a search of a spectrum in a large mass spectral library. In many cases, a library search procedure returns a wrong answer even if a correct compound is contained in a library. In this work, we present a deep learning driven approach to a library search in order to reduce the probability of such cases. Machine learning ranking (learning to rank) is a class of machine learning and deep learning algorithms that perform a comparison (ranking) of objects. This work introduces the usage of deep learning ranking for small molecules identification using low-resolution electron ionization mass spectrometry. Instead of simple similarity measures for two spectra, such as the dot product or the Euclidean distance between vectors that represent spectra, a deep convolutional neural network is used. The deep learning ranking model outperforms other approaches and enables reducing a fraction of wrong answers (at rank-1) by 9-23% depending on the used data set. Spectra from the Golm Metabolome Database, Human Metabolome Database, and FiehnLib were used for testing the model.


Species boundaries and taxonomy of the African river frogs (Amphibia: Pyxicephalidae: Amietia).
A molecular phylogeny of the Afrotropical anuran genus Amietia based on 323 16S sequences indicates that there are 19 species, including four not yet described. No genetic material was available for the nominal A. inyangae. We consider them to represent full species, and define them based on 16S genetic distances, as well as differences in morphology, tadpoles and advertisement call where known. An analysis based on two mitochondrial and two nuclear genes (12S, 16S, 28S and tyrosinase exon 1), from 122 samples, confirmed the phylogenetic relationships suggested by the 16S tree. We recognise and (re-) describe the following species: Amietia angolensis (Bocage, 1866), A. chapini (Noble, 1924), A. delalandii (Duméril & Bibron, 1841), A. desaegeri (Laurent, 1972), A. fuscigula (Duméril & Bibron, 1841), A. hymenopus (Boulenger, 1920), A. inyangae (Poynton, 1966), A. johnstoni (Günther, 1893), A. moyerorum sp. nov., A. nutti (Boulenger, 1896), A. poyntoni Channing & Baptista, 2013, A. ruwenzorica (Laurent, 1972), A. tenuoplicata (Pickersgill, 2007), A. vandijki (Visser & Channing, 1997), A. vertebralis (Hewitt, 1927), and A. wittei (Angel, 1924). Three further candidate species of Larson et al. (2016) await formal naming. We provisionally regard A. amieti (Laurent, 1976) as a junior synonym of A. chapini (Noble, 1924). Amietia lubrica (Pickersgill, 2007) is shown to be a junior synonym of A. nutti, while A. quecketti (Boulenger, 1895) is shown to be a junior synonym of A. delalandii (Duméril & Bibron, 1841), and A. viridireticulata (Pickersgill, 2007) is placed as a junior synonym of A. tenuoplicata (Pickersgill, 2007). On the basis of similarity of 16S sequences, we assign A. sp. 1, A. sp. 3 and A. sp. 6 of Larson et al (2016) to the nomina A. chapini (Noble, 1924), A. desaegeri (Laurent, 1972), and A. nutti (Boulenger, 1896) respectively.


Tunable single-longitudinal-mode ErYb:glass laser locked by a bulk glass Bragg grating.
A single-longitudinal-mode ErYb:glass laser with a linewidth of 90 kHz is demonstrated by locking the laser wavelength to 1552.6 nm with a bulk glass Bragg grating. Using a piezoelectric actuator, the wavelength could be tuned over a range of 0.25 nm (31 GHz) in steps of 17 pm (2.1 GHz), with an output power of a few milliwatts.


Development of infectious clones for virulent and avirulent pichinde viruses: a model virus to study arenavirus-induced hemorrhagic fevers.
Several arenaviruses can cause hemorrhagic fever diseases (VHFs) in humans, the pathogenic mechanism of which is poorly understood due to their virulent nature and the lack of molecular clones. A safe, convenient, and economical small animal model of arenavirus hemorrhagic fever is based on guinea pigs infected by the arenavirus Pichinde (PICV). PICV does not cause disease in humans, but an adapted strain of PICV (P18) causes a disease in guinea pigs that mimics arenavirus hemorrhagic fever in humans in many aspects, while a low-passaged strain (P2) remains avirulent in infected animals. In order to identify the virulence determinants within the PICV genome, we developed the molecular clones for both the avirulent P2 and virulent P18 viruses. Recombinant viruses were generated by transfecting plasmids that contain the antigenomic L and S RNA segments of PICV under the control of the T7 promoter into BSRT7-5 cells, which constitutively express T7 RNA polymerase. By analyzing viral growth kinetics in vitro and virulence in vivo, we show that the recombinant viruses accurately recapitulate the replication and virulence natures of their respective parental viruses. Both parental and recombinant virulent viruses led to high levels of viremia and titers in different organs of the infected animals, whereas the avirulent viruses were effectively controlled and cleared by the hosts. These novel infectious clones for the PICV provide essential tools to identify the virulence factors that are responsible for the severe VHF-like disease in infected animals.


The role of recombinant stem cell factor in early B cell development. Synergistic interaction with IL-7.
The cDNA for stem cell factor was recently isolated from Buffalo rat liver cells (BRL-3A) and recombinant rat stem cell factor produced from Escherichia coli (rrSCF164). rrSCF164 synergizes with rhIL-7 to stimulate pre-B clonal growth in agar culture of mouse bone marrow cells, and in this study we have characterized the role of rrSCF164 in B cell development. The combination of rrSCF164 plus rhIL-7 stimulated increased colony numbers compared with the sum of colonies stimulated by rrSCF164 and rhIL-7 alone. Also, increased cell proliferation per colony was stimulated by the combination of rrSCF164 plus rhIL-7 compared with rhIL-7 or rrSCF164 alone. The colonies formed with rrSCF164 plus rhIL-7 and rhIL-7 alone contained exclusively pre-B cells, which expressed B220 Ag and cytoplasmic mu-chain, but were negative for surface Ig expression. Morphological examination of the cells in the colonies showed blast-like characteristics. rrSCF164 alone and in combination with rhIL-7 stimulated generation of B220+ cells in liquid culture of B220- cells, whereas rhIL-7 alone had no stimulatory effect on B220- cells. Both stem cell factor mRNA and bioactivity were detected in a mouse bone marrow-derived stromal cell line, termed OZ-11. We propose that stem cell factor is a stromal-derived factor that synergizes with IL-7 to stimulate the proliferation and differentiation of pro-B cells to pre-B cells, which become responsive to IL-7 alone.


Research agenda for geriatric rehabilitation.
The Research Agenda Setting Process is a joint endeavor by the American Geriatrics Society and the Hartford Foundation to increase geriatric expertise in the surgical and related specialties. This article provides the results of the Research Agenda Setting Process project on research needs in geriatric rehabilitation, which included a systematic review of the literature and a group consensus process. Explicit research questions and methodologies were developed for three cross-cutting research needs in geriatric rehabilitation and for the rehabilitation of eight specific conditions affecting older individuals.


Focused ultrasound neuromodulation on a multiwell MEA.
Microelectrode arrays (MEA) enable the measurement and stimulation of the electrical activity of cultured cells. The integration of other neuromodulation methods will significantly enhance the application range of MEAs to study their effects on neurons. A neuromodulation method that is recently gaining more attention is focused ultrasound neuromodulation (FUS), which has the potential to treat neurological disorders reversibly and precisely. In this work, we present the integration of a focused ultrasound delivery system with a multiwell MEA plate. The ultrasound delivery system was characterised by ultrasound pressure measurements, and the integration with the MEA plate was modelled with finite-element simulations of acoustic field parameters. The results of the simulations were validated with experimental visualisation of the ultrasound field with Schlieren imaging. In addition, the system was tested on a murine primary hippocampal neuron culture, showing that ultrasound can influence the activity of the neurons. Our system was demonstrated to be suitable for studying the effect of focused ultrasound on neuronal cultures. The system allows reproducible experiments across the wells due to its robustness and simplicity of operation.


Activities, occurrence, and localization of hydrogenase in free-living and symbiotic frankia.
Symbiotic and free-living Frankia were investigated for correlation between hydrogenase activities (in vivo/in vitro assays) and for occurrence and localization of hydrogenase protein by Western blots and immuno-gold localization, respectively. Freshly prepared nodule homogenates from the symbiosis between Alnus incana and a local source of Frankia did not show any detectable in vivo or in vitro hydrogenase uptake activity, as also has been shown earlier. However, a free-living Frankia strain originally isolated from these nodules clearly showed both in vivo and in vitro hydrogenase activity, with the latter being approximately four times higher. Frankia strain Cpl1 showed hydrogen uptake activity both in symbiosis with Alnus incana and in a free-living state. Western blots on the different combinations of host plants and Frankia strains used in the present study revealed that all the Frankia sources contained a hydrogenase protein, even the local source where no in vivo or in vitro activity could be measured. The 72 kilodalton protein found in the symbiotic Frankia as well as in the free-living Frankia strains were immunologically related to the large subunit of a dimeric hydrogenase purified from Alcaligenes latus. Recognitions to polypeptides with molecular masses of about 41 and 19.5 kilodaltons were also observed in Frankia strain UGL011101 and in the local source of Frankia, respectively. Immunogold localization of the protein demonstrated that in both the symbiotic state and the free-living nitrogen-fixing Frankia, the protein is located in vesicles and in hyphae. The inability to measure any uptake hydrogenase activity is therefore not due to the absence of hydrogenase enzyme. However, the possibility of an inactive hydrogenase enzyme cannot be ruled out.


Characterization and Evaluation of Controlled Antimicrobial Release from Petrochemical (PU) and Biodegradable (PHB) Packaging.
The academic exploration and technology design of active packaging are coherently supplying innovative approaches for enhancing the quality and safety of food, as well as prolonging their shelf-life. With the object of comparison between two barrier materials, such as stable petrochemical polyurethane (PU), (BASF), and biodegradable natural poly(3-hydroxybutyrate) (PHB), (Biomer Co., Krailling, Germany), the study of antibacterial agent release has been performed. For the characterization of polymer surface morphology and crystallinity, the scanning electron microscopy (SEM), atomic force microscopy (AFM) and differential scanning calorimetry (DSC) were used respectively. The antimicrobial activity of chlorhexidine digluconate (CHD) has been estimated by the Bauer⁻Kirby Disk Diffusion Test. It was shown that the kinetic release profiles of CHD, as the active agent, in both polymers, significantly differed due to the superposition of diffusion and surface degradation in poly(3-hydroxybutyrate) (PHB). To emphasize the special transport phenomena in polymer packaging, the diffusivity modeling was performed and the CHD diffusion coefficients for the plane films of PU and PHB were further compared. The benefit of active biodegradable packaging on the base of PHB is discussed.


PET/CT for the staging and follow-up of patients with malignancies.
Positron emission tomography (PET) and computed tomography (CT) complement each other's strengths in integrated PET/CT. PET is a highly sensitive modality to depict the whole-body distribution of positron-emitting biomarkers indicating tumour metabolic activity. However, conventional PET imaging is lacking detailed anatomical information to precisely localise pathologic findings. CT imaging can readily provide the required morphological data. Thus, integrated PET/CT represents an efficient tool for whole-body staging and functional assessment within one examination. Due to developments in system technology PET/CT devices are continually gaining spatial resolution and imaging speed. Whole-body imaging from the head to the upper thighs is accomplished in less than 20 min. Spatial resolution approaches 2-4mm. Most PET/CT studies in oncology are performed with (18)F-labelled fluoro-deoxy-D-glucose (FDG). FDG is a glucose analogue that is taken up and trapped within viable cells. An increased glycolytic activity is a characteristic in many types of cancers resulting in avid accumulation of FDG. These tumours excel as "hot spots" in FDG-PET/CT imaging. FDG-PET/CT proved to be of high diagnostic value in staging and restaging of different malignant diseases, such as colorectal cancer, lung cancer, breast cancer, head and neck cancer, malignant lymphomas, and many more. The standard whole-body coverage simplifies staging and speeds up decision processes to determine appropriate therapeutic strategies. Further development and implementation of new PET-tracers in clinical routine will continually increase the number of PET/CT indications. This promotes PET/CT as the imaging modality of choice for working-up of the most common tumour entities as well as some of the rare malignancies.


Analysis of SARS-CoV-2 ORF3a structure reveals chloride binding sites.
SARS-CoV-2 ORF3a is believed to form ion channels, which may be involved in the modulation of virus release, and has been implicated in various cellular processes like the up-regulation of fibrinogen expression in lung epithelial cells, downregulation of type 1 interferon receptor, caspase-dependent apoptosis, and increasing IFNAR1 ubiquitination. ORF3a assemblies as homotetramers, which are stabilized by residue C133. A recent cryoEM structure of a homodimeric complex of ORF3a has been released. A lower-resolution cryoEM map of the tetramer suggests two dimers form it, arranged side by side. The dimer's cryoEM structure revealed that each protomer contains three transmembrane helices arranged in a clockwise configuration forming a six helices transmembrane domain. This domain's potential permeation pathway has six constrictions narrowing to about 1 Å in radius, suggesting the structure solved is in a closed or inactivated state. At the cytosol end, the permeation pathway encounters a large and polar cavity formed by multiple beta strands from both protomers, which opens to the cytosolic milieu. We modeled the tetramer following the arrangement suggested by the low-resolution tetramer cryoEM map. Molecular dynamics simulations of the tetramer embedded in a membrane and solvated with 0.5 M of KCl were performed. Our simulations show the cytosolic cavity is quickly populated by both K+ and Cl-, yet with different dynamics. K+ ions moved relatively free inside the cavity without forming proper coordination sites. In contrast, Cl- ions enter the cavity, and three of them can become stably coordinated near the intracellular entrance of the potential permeation pathway by an inter-subunit network of positively charged amino acids. Consequently, the central cavity's electrostatic potential changed from being entirely positive at the beginning of the simulation to more electronegative at the end.


Transcriptional activity of pannier is regulated negatively by heterodimerization of the GATA DNA-binding domain with a cofactor encoded by the u-shaped gene of Drosophila.
The genes pannier (pnr) and u-shaped (ush) are required for the regulation of achaete-scute during establishment of the bristle pattern in Drosophila. pnr encodes a protein belonging to the GATA family of transcription factors, whereas ush encodes a novel zinc finger protein. Genetic interactions between dominant pnr mutants bearing lesions situated in the amino-terminal zinc finger of the GATA domain and ush mutants have been described. We show here that both wild-type Pannier and the dominant mutant form activate transcription from the heterologous alpha globin promoter when transfected into chicken embryonic fibroblasts. Furthermore, Pnr and Ush are found to heterodimerize through the amino-terminal zinc finger of Pnr and when associated with Ush, the transcriptional activity of Pnr is lost. In contrast, the mutant pnr protein with lesions in this finger associates only poorly with Ush and activates transcription even when cotransfected with Ush. These interactions have been investigated in vivo by overexpression of the mutant and wild-type proteins. The results suggest an antagonistic effect of Ush on Pnr function and reveal a new mode of regulation of GATA factors during development.


Establishment of surgery satellite pharmacy services in a large community hospital.
Implementation of a satellite pharmacy serving the operating rooms (OR) and recovery areas in a nonteaching, 676-bed community hospital is described. Justification for proposed services are listed. Objectives and the steps taken in the implementation and maintenance of the services are described. Objectives were: (1) increased accountability of drug distribution and control; (2) improved accuracy in recording of patient charges; (3) improved accuracy in charting of medications administered; (4) adoption of a standardized anesthesiology medication system implemented on a kit-per-case basis; (5) enhancement of the pharmacy image through the improved provision of cost containing pharmacy services; and (6) promotion of improved patient care through a health care team approach.


Tissue engineering applications in otolaryngology-The state of translation.
While tissue engineering holds significant potential to address current limitations in reconstructive surgery of the head and neck, few constructs have made their way into routine clinical use. In this review, we aim to appraise the state of head and neck tissue engineering over the past five years, with a specific focus on otologic, nasal, craniofacial bone, and laryngotracheal applications. A comprehensive scoping search of the PubMed database was performed and over 2000 article hits were returned with 290 articles included in the final review. These publications have addressed the hallmark characteristics of tissue engineering (cellular source, scaffold, and growth signaling) for head and neck anatomical sites. While there have been promising reports of effective tissue engineered interventions in small groups of human patients, the majority of research remains constrained to in vitro and in vivo studies aimed at furthering the understanding of the biological processes involved in tissue engineering. Further, differences in functional and cosmetic properties of the ear, nose, airway, and craniofacial bone affect the emphasis of investigation at each site. While otolaryngologists currently play a role in tissue engineering translational research, continued multidisciplinary efforts will likely be required to push the state of translation towards tissue-engineered constructs available for routine clinical use. NA.


Signal Transmission of Biological Reaction-Diffusion System by Using Synchronization.
Molecular signal transmission in cell is very crucial for information exchange. How to understand its transmission mechanism has attracted many researchers. In this paper, we prove that signal transmission problem between neural tumor molecules and drug molecules can be achieved by synchronous control. To achieve our purpose, we derive the Fokker-Plank equation by using the Langevin equation and theory of random walk, this is a model which can express the concentration change of neural tumor molecules. Second, according to the biological character that vesicles in cell can be combined with cell membrane to release the cargo which plays a role of signal transmission, we preliminarily analyzed the mechanism of tumor-drug molecular interaction. Third, we propose the view of synchronous control which means the process of vesicle docking with their target membrane is a synchronization process, and we can achieve the precise treatment of disease by using synchronous control. We believe this synchronous control mechanism is reasonable and two examples are given to illustrate the correctness of our results obtained in this paper.


Regulation of Cytoplasmic and Vacuolar pH in Maize Root Tips under Different Experimental Conditions.
(31)P-Nuclear magnetic resonance spectra of perfused maize (Zea mays L., hybrid WW x Br 38) root tips, obtained at 10-minute intervals over 12 hours or longer, indicate that no cytoplasmic or vacuolar pH changes occur in these cells in the presence of 25 millimolar K(2)SO(4), which induces extrusion of 4 to 5 microequivalents H(+) per gram per hour. In contrast, hypoxia causes cytoplasmic acidification (0.3-0.6 pH unit) without a detectable change in vacuolar pH. The cytoplasm quickly returns to its original pH on reoxygenation. Dilute NH(4)OH increases the vacuolar pH more than it does the cytoplasmic pH; after NH(4)OH is removed, the vacuole recovers its original pH more slowly than does the cytoplasm. The results indicate that regulation of cytoplasmic pH and that of vacuolar pH in plant cells are separate processes.


Magnetization transfer MR imaging demonstrates degeneration of the subcortical and cortical gray matter in Huntington disease.
GM is typically affected in HD since the presymptomatic stage. Our aim was to investigate with MT MR imaging the microstructural changes of the residual brain subcortical and cortical GM in carriers of the HD gene and to preliminarily assess their correlation with the clinical features. Fifteen HD gene carriers with a range of clinical severity and 15 age- and sex-matched healthy controls underwent MT MR imaging on a 1.5T scanner. The MT ratio was measured automatically in several subcortical and cortical GM regions (striatal nuclei; thalami; and the neocortex of the frontal, temporal, parietal, and occipital lobes) by using FLS tools. The MT ratio was significantly (P < .05 with Bonferroni correction for multiple comparison) decreased in all subcortical structures except the putamen and decreased diffusely in the cerebral cortex of HD carriers compared with controls. Close correlation was observed between the subcortical and cortical regional MT ratios and several clinical variables, including disease duration, motor disability, and scores in timed neuropsychological tests. MT imaging demonstrates degeneration of the subcortical and cortical GM in HD carriers and might serve, along with volumetric assessment, as a surrogate marker in future clinical trials of HD.


Hydrogen storage in microporous metal-organic frameworks with exposed metal sites.
Owing to their high uptake capacity at low temperature and excellent reversibility kinetics, metal-organic frameworks have attracted considerable attention as potential solid-state hydrogen storage materials. In the last few years, researchers have also identified several strategies for increasing the affinity of these materials towards hydrogen, among which the binding of H(2) to unsaturated metal centers is one of the most promising. Herein, we review the synthetic approaches employed thus far for producing frameworks with exposed metal sites, and summarize the hydrogen uptake capacities and binding energies in these materials. In addition, results from experiments that were used to probe independently the metal-hydrogen interaction in selected materials will be discussed.


Signal transduction by a nondissociable heterotrimeric yeast G protein.
Many signal transduction pathways involve heterotrimeric G proteins. The accepted model for activation of heterotrimeric G proteins states that the protein dissociates to the free G(alpha) (GTP)-bound subunit and free G(betagamma) dimer. On GTP hydrolysis, G(alpha) (GDP) then reassociates with G(betagamma) [Gilman, A. G. (1987) Annu. Rev. Biochem. 56, 615-649]. We reexamined this hypothesis, by using the mating G protein of the yeast Saccharomyces cerevisiae encoded by the genes GPA1, STE4, and STE18. In the absence of mating pheromone, the G(alpha) (Gpa1) subunit represses the mating pathway. On activation by binding of pheromone to a serpentine receptor, the G(betagamma) (Ste4, Ste18) dimer transmits the signal to a mitogen-activated protein kinase cascade, leading to gene activation, arrest in the G(1) stage of the cell cycle, production of shmoos (mating projections), and cell fusion. We found that a Ste4-Gpa1 fusion protein transmitted the pheromone signal and activated the mating pathway as effectively as when Ste4 (G(beta)) and Gpa1 (G(alpha)) were coexpressed as separate proteins. Hence, dissociation of this G protein is not required for its activation. Rather, a conformational change in the heterotrimeric complex is likely to be involved in signal transduction.


Accidental detection of nonmetastatic ovarian adenocarcinoma in tissue samples recovered during dilatation and curettage.
We report two patients with ovarian cancer who were diagnosed with primary endometrial cancer when detached fragments of adenocarcinoma were identified in their dilatation and curettage specimens. Retrospectively, a fragment of fallopian tube and ovarian stroma were identified in the specimens. These findings served to alert the pathologist to the possibility that extrauterine sampling had occurred as a result of perforation of uterine wall during dilatation and curettage. Previous studies have focused on the cytologic detection of extrauterine cancer or on cases where metastasis to the endometrium has led to a misdiagnosis of primary endometrial cancer.


Continuous spirometry: an aid to monitoring ventilation during operation.
We present six case-reports of patients who experienced inadequate ventilation as a result of endobronchial or oesophageal intubation, or obstruction to the tracheal tube or airway and were monitored with on-line spirometry. The continuously displayed pressure-volume or flow-volume loops may be compared with previously recorded baseline loops. The changing configuration of the curves offers additional and instantaneous information about the cause of increased inspiratory airway pressure, decreased compliance or increased airway resistance. Monitoring flow-volume and pressure-volume loops in conjunction with currently available techniques provides a comprehensive method of monitoring ventilation.


[Cannabinoid hyperemesis as a differential diagnosis of nausea and vomiting in the emergency department].
Cannabinoid hyperemesis syndrome (CHS) is caused by regular cannabis consumption and marked by cyclic episodes of severe emesis, often years after the beginning of cannabis consumption. Classical antiemetic treatment often shows no effect and fatal outcomes have sometimes also been reported. This article describe the case of a young man in whom the diagnosis was made after four presentations due to the typical anamnesis. At this point in time he had already undergone an abdominal computed tomography (CT) and gastroscopy, both with no pathological findings. The symptoms completely receded 6 months after presentation by maintaining cannabis abstinence.


Expression of the NSE,SP,NFH and DβH in normal and cryptorchid testes of Bactrian camel.
Neuroendocrine substances play essential roles in regulating the normal physiological functions of testicles. The purpose of this study is to explore the localization and effects of four neuroendocrine markers (NSE, SP, NFH and DβH) in normal and cryptorchid testes of Bactrian camels using western blotting, transmission electron microscopy, immunohistochemistry, and immunofluorescence methods. The results showed that cryptorchidism caused a reduction in layers of spermatogenic epithelium and decreased glycogen positivity in the basement membrane. The ultrastructure revealed that macrophages were always found around the Leydig cells, crowded with swelling mitochondria in cryptorchidism. Expression of NSE in the Leydig cells of cryptorchidism was significantly weakened compared to that in the normal group(p<0.01). We found that SP was always distributed along the nerve fibers in normal testes and was expressed in the Leydig cells of cryptorchidism. However, expression of NFH in the cryptorchidic tissue was strongly positive in the spermatogenic epithelium, with limited expression in Leydig cells and no expression in peritubular myoid cells. Therefore, the expression of DβH in the Sertoli cells was comparatively strong in both the normal and cryptorchidism groups. NFH and DβH expression was significantly increased in the cryptorchidism group compared with the normal group (p<0.01). These findings indicated that the underdeveloped seminiferous epithelium and pathological changes in cryptorchid tissue in Bactrian camels were potentially related to a disorder in glycoprotein metabolism. Our results suggest that NSE and SP could help judge the pathological changes of cryptorchidism. The present study provides the first evidence at the protein level for the existence of NFH and DβH in Sertoli and Leydig cells in Bactrian camel cryptorchidism and provides a more in-depth understanding of neuroendocrine regulation is crucial for animal cryptorchidism.


Alkaloid binding and activation of D2 dopamine receptors in cell culture.
Ergot and pyrrolizidine alkaloids, either extracted from endophyte-infected tall fescue, synthesized, or purchased commercially, were evaluated in cultured cells to estimate their binding to the D2 dopamine receptor and subsequent effects on cyclic AMP production in GH4ZR7 cells, transfected with a rat D2 dopamine receptor. Ergopeptide alkaloid (alpha-ergocryptine, bromocryptine, ergotamine tartrate, and ergovaline) inhibition of the binding of the D2-specific radioligand, [3H]YM-09151-2, exhibited inhibition constants (K(I)) in the nanomolar range, whereas dopamine was less potent (micromolar). The lysergic acid amides (ergine and ergonovine) were 1/100th as potent as the ergopeptide alkaloids. Ergovaline and ergotamine tartrate were equally effective in inhibiting vasoactive intestinal peptide (VIP)-stimulated cyclic AMP production, with consistent nanomolar effective concentration (EC50) values. The remaining ergopeptide alkaloids (alpha-ergocryptine and bromocryptine), lysergic acid amides (ergonovine and ergine), and dopamine were 1/100th as potent. Two representative pyrrolizidines, N-formylloline and N-acetylloline, exhibited no binding activity at the D2 dopamine receptor or effects on the cyclic AMP system within the concentration ranges of nanomolar to millimolar. Our results indicate that the commercially available ergot alkaloids ergotamine tartrate and ergonovine may be used interchangeably in the D2 dopamine receptor system to simulate the effects of extracted ergovaline and ergine and to examine responses in receptor binding and the inhibition of cyclic AMP.


Proton Magnetic Resonance Spectroscopy-Detected Changes of Marrow Fat Content in a Rabbit Model of Osteoporosis Treated With Epigallocatechin-3-Gallate.
The aim of this study was to longitudinally evaluate the changes in marrow fat content of ovariectomized (OVX) rabbits treated with epigallocatechin-3-gallate (EGCG) using proton magnetic resonance spectroscopy (H-MRS). Thirty-six female New Zealand rabbits were equally divided into sham operation, OVX controls, and OVX treated with EGCG (intraperitoneally, 1.8 mg/kg) for 5 months. Marrow fat fraction by H-MRS and bone density by peripheral quantitative computed tomography were determined at 0, 3, and 5 months. Serum biomarkers and marrow adipocytes were determined at the end of experiment. Estrogen deficiency increased marrow fat content in a time-dependent manner, with a variation of marrow fat fraction (FF) (+25.3%) at month 3 from baseline, and it was maintained until month 5 (+66.6%, all P < 0.001). In comparison with the sham-operated controls, adipocytes density, size, and percentage of adipocytes area in the OVX controls increased by 62.9%, 44.4%, and 178%, respectively (all P < 0.05). These OVX-induced pathological changes were partly reversed by EGCG treatment. In addition, EGCG treatment reduced bone turnover and increased bone density of OVX rabbits. Epigallocatechin-3-gallate exhibits an anabolic effect on osteoporotic bone by concomitantly rescuing bone mass and mitigating marrow adiposity. H-MRS appears to be a useful tool for monitoring osteoporosis-related treatments.


Loss-of-function variants in myocardin cause congenital megabladder in humans and mice.
Myocardin (MYOCD) is the founding member of a class of transcriptional coactivators that bind the serum-response factor to activate gene expression programs critical in smooth muscle (SM) and cardiac muscle development. Insights into the molecular functions of MYOCD have been obtained from cell culture studies, and to date, knowledge about in vivo roles of MYOCD comes exclusively from experimental animals. Here, we defined an often lethal congenital human disease associated with inheritance of pathogenic MYOCD variants. This disease manifested as a massively dilated urinary bladder, or megabladder, with disrupted SM in its wall. We provided evidence that monoallelic loss-of-function variants in MYOCD caused congenital megabladder in males only, whereas biallelic variants were associated with disease in both sexes, with a phenotype additionally involving the cardiovascular system. These results were supported by cosegregation of MYOCD variants with the phenotype in 4 unrelated families by in vitro transactivation studies in which pathogenic variants resulted in abrogated SM gene expression and by the finding of megabladder in 2 distinct mouse models with reduced Myocd activity. In conclusion, we have demonstrated that variants in MYOCD result in human disease, and the collective findings highlight a vital role for MYOCD in mammalian organogenesis.


The effect of drought on mycorrhizas of beech (Fagus sylvatica L.): changes in community structure, and the content of carbohydrates and nitrogen storage bodies of the fungi.
In a water-exclusion experiment, five different ecotypes of beech (Fagus sylvatica L.; representing regions of different environmental and climatic conditions in Baden-Württemberg, Germany) were subjected to drought conditions of different severity between July and September of two consecutive years. Drought stress as characterised by the water content and the pre-dawn water potential of the leaves was related to the degree of mycorrhization, the type of ectomycorrhiza, and the physiological properties of individual fungus/plant interactions at the fine roots of different beech ecotypes. Our data show that decreased soil water availability did not significantly change either the degree of fungal colonisation of beech roots (measured by the amount of ergosterol) or the number of ectomycorrhizal types per root system. Drought did, however, have an influence on the composition of the ectomycorrhizal community, and different mycorrhizal types responded to drought differently in terms of their patterns of occurrence/abundance. While the abundance of the dominant mycorrhizal types, formed with Byssocorticium atrovirens and Lactarius subdulcis, was not affected, drought increased the abundance of mycorrhiza formed between beech and Xerocomus chrysenteron. A detailed analysis of plant and fungal carbohydrates in mycorrhizas indicated that different drought intensities led to distinguishable responses. In plants exhibiting a pre-dawn water potential of down to -1.96 MPa, drought caused the accumulation of sucrose, glucose and fructose, and of fungus-specific compounds such as mannitol and arabitol in mycorrhizal roots at the expense of, e.g. trehalose. The accumulation of sugar alcohols, which constitute compatible solutes known to counteract drought stress, was species-specific. Mycorrhizas with X. chrysenteron formed large amounts of arabitol, while those with L. subdulcis accumulated mannitol. Sustained partitioning of carbon towards the mycorrhizal fungi under drought was also reflected by an increase of nitrogen storage in the fungal vacuoles. In treatments where the pre-dawn water potential reached values of as low as -2.4 MPa, such alterations were no longer found. In such plants, the starch and soluble sugars content was generally reduced, which also resulted in a lack of increase in protective, fungus-specific sugar alcohols. In summary, the data show that, within certain limits, an increase in drought causes a shift in plant/fungus communities. The shift in the pattern of fungus-specific compounds could possibly be used as a sensitive measure of physiological stress imposed on this symbiosis.


Fast Markov Clustering Algorithm Based on Belief Dynamics.
Graph clustering is one of the most significant, challenging, and valuable topic in the analysis of real complex networks. To detect the cluster configuration accurately and efficiently, we propose a new Markov clustering algorithm based on the limit state of the belief dynamics model. First, we present a new belief dynamics model, which focuses beliefs of multicontent and randomly broadcasting information. A strict proof is provided for the convergence of nodes' normalized beliefs in complex networks. Second, we introduce a new Markov clustering algorithm (denoted as BMCL) by employing a belief dynamics model, which guarantees the ideal cluster configuration. Following the trajectory of the belief convergence, each node is mapped into the corresponding cluster repeatedly. The proposed BMCL algorithm is highly efficient: the convergence speed of the proposed algorithm researches O(TN) in sparse networks. Last, we implement several experiments to evaluate the performance of the proposed methods.


1-trityl-4-nitroimidazole.
X-ray analysis confirmed the configuration of the title N1-alkylated C4-nitroimidazole inhibitor. The plane of the imidazole ring, sitting on an axis of the trityl propeller, bisects the angle between two phenyl rings, while the nitro group extends over the third. Modeling of the interactions between the cytochrome P450 and the title compound (C22H17N3O2) has been performed on the basis of the crystal structures of 1-trityl-4-nitroimidazole and bacterial cytochrome P450BM-3. The replacements and deletions in the sequence of the latter has been performed to match mammalian cytochrome P450-IIIA1. The modeling explained why inhibitors with a C4-substituted imidazole ring showed lower effectivity than those without substituents, as an additional group of atoms at C4 prevents close interactions of the imidazole ring with the heme Fe atom.


Becoming and remaining community health workers: perspectives from Ethiopia and Mozambique.
Many global health practitioners are currently reaffirming the importance of recruiting and retaining effective community health workers (CHWs) in order to achieve major public health goals. This raises policy-relevant questions about why people become and remain CHWs. This paper addresses these questions, drawing on ethnographic work in Addis Ababa, the capital of Ethiopia, between 2006 and 2009, and in Chimoio, a provincial town in central Mozambique, between 2003 and 2010. Participant observation and in-depth interviews were used to understand the life histories that lead people to become CHWs, their relationships with intended beneficiaries after becoming CHWs, and their social and economic aspirations. People in Ethiopia and Mozambique have faced similar political and economic challenges in the last few decades, involving war, structural adjustment, and food price inflation. Results suggest that these challenges, as well as the socio-moral values that people come to uphold through the example of parents and religious communities, influence why and how men and women become CHWs. Relationships with intended beneficiaries strongly influence why people remain CHWs, and why some may come to experience frustration and distress. There are complex reasons why CHWs come to seek greater compensation, including desires to escape poverty and to materially support families and other community members, a sense of deservingness given the emotional and social work involved in maintaining relationships with beneficiaries, and inequity vis-à-vis higher-salaried elites. Ethnographic work is needed to engage CHWs in the policy process, help shape new standards for CHW programs based on rooting out social and economic inequities, and develop appropriate solutions to complex CHW policy problems.


Interactive television presentation style and teaching materials.
Special teaching techniques and presentation style are required for an effective telecourse. This article describes modification of a traditional graduate nursing course for televised delivery to remote students. Teacher appearance and behaviors as well as student activities for telecourses are proposed.


Vectorettes for long chromosome walking in genomic DNA of the human p53 gene.
Chromosome walking in mammalian DNA by vectorette PCR is not always very specific, and the walks have been limited to distances <1 kb. To improve the method, we have designed new vectorettes, which unlike the currently used ones have very little repetitive sequences or homology with known DNA sequences of various origins in the data banks. We have tested these new vectorettes for chromosome walking in human p53 tumor suppressor gene, human tissue-type plasminogen activator gene, and mouse stanniocalcin gene with good success. In chromosome walking of the human p53 gene, we isolated gene-specific fragments of 2.4. kb, and by walking in a bacterial artificial chromosome (BAC) clone carrying the mouse stanniocalcin gene, we isolated fragments up to about 7 kb in size. We further sequenced the 5' region of the p53 gene and found that the nucleotides upstream of -1009 are transcribed in antisense orientation into a messenger RNA (mRNA) (flj10385) encoding a putative serine/threonine kinase.


Transurethral Drainage of Prostatic Abscess Using 120 W Holmium Laser Technology.
Introduction: Prostatic abscess is an infrequent but serious pathology that could be treated by ultrasound-guided puncture, transurethral resection, or open surgery. Case Report: We present a case of a 72-year-old male with a 3x5 cm prostatic abscess in the right lobe showed in abdominal computed tomography (CT). In the blood test, he presented coagulopathy. Urgent transurethral drainage by holmium laser was decided to be performed. It started with incision and opening of the right prostatic lobe with an energy of 1.2 J and a frequency of 20 Hz with a total power of 24 W. A 550-micron fiber was used for this technique. Coagulation of the area was performed with a power of 20 W. The postoperative course was uneventful. Conclusion: The holmium laser appears to be an effective alternative in the treatment of this pathology in patients with coagulation disorders by providing adequate hemostatic control.


Deletion analysis of a 2S seed storage protein promoter of Brassica napus in transgenic tobacco.
The promoter and upstream region of the Brassica napus 2S storage protein napA gene were studied to identify cis-acting sequences involved in developmental seed-specific expression. Fragments generated by successive deletions of the 5' control region of the napA gene were fused to the reporter gene beta-glucuronidase (GUS). These constructs were used to transform tobacco leaf discs. Analyses of GUS activities in mature seeds from the transformed plants indicated that there were both negatively and positively acting sequences in the napin gene promoter. Deletion of sequences between -1101 and -309 resulted in increased GUS activity. In contrast, deletion of sequences between -309 and -211 decreased the expression. The minimum sequence required for seed-specific expression was a 196 bp fragment between -152 and +44. Further 5' deletion of the fragment to -126 abolished this activity. Sequence comparison showed that a G box-like sequence and two sequence motifs conserved between 2S storage protein genes are located between -148 to -120. Histochemical and fluorometric analysis of tobacco seeds showed that the spatial and developmental expression pattern was retained in the deletion fragments down to -152. However, the expression in tobacco seeds differed from the spatial and temporal expression in B. napus. In tobacco, the napA promoter directed GUS activity early in the endosperm before any visible activity could be seen in the heart-shaped embryo. Later, during the transition from heart to torpedo stages, the main expression of GUS was localized to the embryo. No significant GUS activity was found in either root or leaf.


Dose-response relationship between lower serum magnesium level and higher prevalence of knee chondrocalcinosis.
The aim was to assess serum magnesium levels in relation to prevalence of knee chondrocalcinosis in two population-based Chinese studies. Data included in this analysis consisted of two population-based cross-sectional studies, i.e., the Xiangya Hospital Health Management Center Study and the Xiangya Osteoarthritis (XO) Study I. A bilateral knee anteroposterior radiograph was obtained from each subject. Radiographic knee chondrocalcinosis was present if there was definite linear cartilage calcification. Serum magnesium concentration was measured using the chemiluminescence method. We examined the relation of serum magnesium levels to prevalence of knee chondrocalcinosis using generalized estimating equations. The prevalence of knee chondrocalcinosis was 1.4% in the Xiangya Hospital Health Management Center Study (n = 12,631). Compared with the lowest tertile, the age, sex and body mass index (BMI)-adjusted odds ratios (ORs) of chondrocalcinosis were 0.59 (95% CI 0.40-0.87) and 0.49 (95% CI 0.33-0.72) in the second and the third tertiles of serum magnesium, respectively (P for trend <0.001). The prevalence of knee chondrocalcinosis in the XO Study I (n = 1316) was 4.1%. The age, sex and BMI-adjusted ORs of chondrocalcinosis were 0.67 (95% CI 0.34-1.30) in the second and 0.45 (95% CI 0.21-0.94) in the third tertile of serum magnesium when compared with the lowest tertile (P for trend = 0.030). Similar results were observed in men and women in both studies. Adjusting for additional potential confounders did not change the results materially. Subjects with lower levels of serum magnesium, even within the normal range, had higher prevalence of knee chondrocalcinosis in a dose-response relationship manner, suggesting that magnesium may have a preventive or therapeutic potential for knee chondrocalcinosis.


Atomic charge states in a weakly coupled plasma environment.
The relative stability of various charge states of a number of selected elements has been studied as a function of increasing screening due to a weakly bound plasma represented by the statically screened Coulomb potential of the Yukawa-type. Elements with positive electron affinity in a vacuum are predicted to undergo a sequential electron detachment process from anionic state to the cationic one as the inverse screening length of plasma increases. Conversely, elements with negative electron affinity in a vacuum present only two charge states, neutral and positive. At small screening the neutral is the most stable charge state, and as the screening increases the cation develops as the most stable charge state. Values of the inverse screening length for each of the transitions have been calculated and discussed.


Waiting time and mortality rate on lung transplant candidates in Japan: a single-center retrospective cohort study.
As lung transplantation (LTX) is a valuable treatment procedure for end-stage pulmonary disease, delayed referral to a transplant center should be avoided. We aimed to conduct a single-center analysis of the survival time after listing for LTX and waitlist mortality in each disease category in a Japanese population. We included patients listed for LTX at Tohoku University Hospital from January 2007 to December 2020 who were followed up until March 2021. Pulmonary disease was categorized into the Obstructive, Vascular, Suppurative, Fibrosis, and Allogeneic groups. Risk factors for waitlist mortality were assessed using a Cox proportional hazards model. The Kaplan-Meier method was used to model time to death. We included 269 LTX candidates. Of those, 100, 72, and 97 patients were transplanted, waiting, and dead, respectively. The median time to LTX and time to death were 796 days (interquartile range [IQR] 579-1056) and 323 days (IQR 129-528), respectively. The Fibrosis group showed the highest mortality (50.9%; p < .001), followed by the Allogeneic (35.0%), Suppurative (33.3%), Vascular (32.1%), and Obstructive (13.1%) groups. The Fibrosis group showed a remarkable risk for waitlist mortality (hazard ratio 3.32, 95% CI 2.11-4.85). In Japan, the waiting time is extremely long and candidates with Fibrosis have high mortality. There is a need to document outcomes based on the underlying disease for listed LTX candidates to help determine the optimal timing for listing patients based on the estimated local waiting time.


Meningococcal Carriage in 'Men Having Sex With Men' With Pharyngeal Gonorrhoea.
We assessed the characteristics of Neisseria meningitidis pharyngeal carriage in a cohort of 'men having sex with men', including patients with pharyngeal Neisseria gonorrhoeae infection. In the period 2017-2019, among all the oropharyngeal samples tested for gonorrhoea from MSM attending a STI Clinic in Bologna (Italy), we randomly selected 244 N. gonorrhoeae-positive samples and 403 negatives (n=647). Pharyngeal specimens were tested for N. meningitidis presence, by the detection of sodC gene. N. meningitidis-positive samples were further grouped by PCR tests for the major invasive genogroups (i.e., A, B, C, W, and Y). A molecular assay, targeting capsule transporter gene, was used to determine meningococcal capsular status. Overall, 75.8% (491/647) of samples tested positive for sodC gene, indicating a pharyngeal meningococcal carriage. Meningococcal colonisation was significantly more frequent in younger subjects (P=0.009), with no association with HIV infection. Non-groupable meningococci represented most of pharyngeal carriages (about 71%). The commonest N. meningitidis serogroup was B (23.6%), followed by C (2.1%), Y (1.8%) and W (1.1%). Meningococci were often characterized by the genetic potential of capsule production. Interestingly, a negative association between N. meningitidis and N. gonorrhoeae was found: pharyngeal gonorrhoea was significantly more present in patients without meningococcal carriage (P=0.03). Although preliminary, our data added knowledge on the epidemiology of meningococcal carriage in MSM communities at high risk of gonococcal infections, gaining new insights into the interactions/dynamics between N. meningitidis and N. gonorrhoeae.


Sperm-zona binding and sperm-oocyte penetration analysed by DNA fluorescence: a test for gamete quality after in-vitro fertilization.
Sperm-zona binding, sperm-oocyte penetration and pronucleus formation in oocytes obtained after in-vitro fertilization (IVF) failure were studied by analysing DNA fluorescence. Oocytes were classified according to their maturational status, sperm-zona pellucida binding and sperm-oocyte penetration. Spermatozoa were classified as normal or abnormal according to conventional parameters. Sperm-zona binding and sperm-oocyte penetration into uncleaved oocytes were positively related to fertilization: 6.2% of those oocytes from cohorts where none of the oocytes fertilized had > 10 spermatozoa bound to the zona, and 7.7% of them were penetrated. When at least one oocyte per cohort fertilized, these rates were 37.1 and 41.1% respectively. Sperm-zona binding is related more strongly to sperm-oocyte penetration, even without pronucleus formation, than to the maturational status of the oocyte: 26.9% of the oocytes were penetrated by spermatozoa, of which 20.7% had reached the pronuclear stage. For 25 out of 78 couples with a total IVF failure, whatever the spermiogram, defective sperm-zona binding, sperm-oocyte penetration or pronucleus formation was observed. Sperm-zona binding and penetration were positively related, especially when oocytes came from patients with partial IVF failure. Clinical information concerning the fertilizing capacity of oocytes and spermatozoa after IVF failure can be obtained by the simultaneous analysis of sperm-zona binding and sperm-oocyte penetration, and whether or not the latter results in pronucleus formation.


Characterization of subpopulations and immune-related parameters of hemocytes in the green-lipped mussel Perna viridis.
The green-lipped mussel Perna viridis is distributed widely in the estuarine and coastal areas of the Indo-Pacific region and extensively cultured as an inexpensive protein source. Morphology and immunological activities of hemocytes of P. viridis were investigated using flow cytometry and light and electron microscopy. Three major types of hemocytes were identified in the hemolymph, including dense-granulocyte, semi-granulocyte (small and large size) and hyalinocyte. Other hemocytes, which occurred in low numbers, included granulocytes with different electron-dense/lucent granules and hemoblast-like cells. Based on flow cytometry, two subpopulations were identified. Granulocytes were larger cells, and the more abundant, containing numerous granules in the cytoplasm, and hyalinocytes were the smaller and less abundant with the fewest granules. Flow cytometry revealed that the granulocytes were more active in cell phagocytosis, contained the higher lysosomal content, and showed higher esterase activity and reactive oxygen species (ROS) generation compared with hyalinocytes. Immune functions assessed by the flow cytometry indicated that the granulocytes were the main hemocytes involved in the cellular defence in P. viridis.


Effect of GABA-ergic drugs on flunarizine-induced seizures in rabbits.
In this study the authors have evaluated the effects of common antiepileptic drugs given alone or in combinations with baclofen on seizures evoked by intravenous flunarizine in rabbits. The abolition of clonic and clonic-tonic convulsions was taken as the end point. Baclofen was able to inhibit convulsions only in a relatively high dose (5 mg/kg). Diazepam (1.5 mg/kg) and clonazepam (2 mg/kg) completely abolished clonic seizures. Valproate (20 mg/kg) inhibited clonic seizures and remained without effect on tonic convulsions. Other antiepileptics such as carbamazepine and acetazolamide were found inactive in this respect. Moreover, combinations of acetazolamide (100 mg/kg) and carbamazepine (50 mg/kg) with baclofen (2 mg/kg) had no anticonvulsant effect. Thus, mainly GABA modulatory drugs reveal significant action against flunarizine-induced seizures.


Granulocyte transfusion.
Granulocyte transfusions have been used for more than four decades. Several issues have complicated the analysis of previous studies, including the utilization of improved antimicrobials, the effects of recipient alloimmunization and variable cell dose. The use of granulocyte colony-stimulating factor for donor stimulation has revived interest in granulocyte transfusion. The aim of this review is to evaluate the most recent studies in granulocyte transfusion therapy and their clinical applicability. Granulocyte colony-stimulating factor use has increased the granulocyte yield by approximately fourfold. Multiple recent studies have shown that granulocyte transfusions can be helpful in controlling severe infections progressing despite the use of appropriate antibiotics, with a response rate of 40-80% with variability in results depending on patient characteristics. This benefit is limited to a small patient population as the incidence of prolonged reversible neutropenia is relatively small. Severe side effects have been rare in those studies. Granulocyte transfusions are beneficial in neutropenic patients with severe uncontrolled infection. The underlying disease process is the major determinant of outcome in these patients. Because granulocyte transfusions are not commonly used, centers are not currently able to provide transfusions in a timely fashion. Nonalloimmunized patients can receive cells from nonmatched ABO compatible donors, while alloimmunized patients should receive granulocytes from either HLA-matched donors or donors selected by leukoagglutination or lymphocytotoxicity crossmatching. Further studies are needed to clarify the optimal starting time and frequency of transfusions, and the best method for identifying donor-recipient compatibility.


Pigment synthesizing melanoma (so-called animal type melanoma): a clinicopathological study of 14 cases of a poorly known distinctive variant of melanoma.
Pigment synthesizing melanoma (so-called animal type melanoma) (PSM) is a rare histopathological variant of melanoma so termed because of prominent melanin production and its similarity to a variant of melanoma seen in grey horses. The aim of this study was to report the clinicopathological characteristics of 14 cases of animal type melanoma. Six patients were female and eight were male with ages ranging from 5 to 52 years (mean 31 years, median 39 years). The head and neck represented the most common site. The clinical diagnosis was of melanoma in seven cases, blue naevus in three cases, benign naevus in three cases and a pigmented basal cell carcinoma in one case. The histological diagnosis of PSM was predicated on the basis of an asymmetrical, predominantly intradermal tumour formed of deeply pigmented, round or short, spindle-shaped dendritic melanocytes with some degree of hyperchromatism and a single nucleolus. Cytological atypia was always present but was not pronounced. A prominent population of macrophages was invariably present. Four tumours were compound and 10 tumours were predominantly intradermal. The mitotic count was usually low, ranging from 1 to 5 per 10 high-power fields (mean 2). Perineural and lymphovascular invasion was not seen. The Breslow thickness ranged from 1.1 to 7.5 mm (mean 3.3 mm). Follow-up was available in 13 patients. The median follow-up period was 5 years. Six patients had no recurrence, three had local recurrence in the form of satellite nodules adjacent to the scar, four had spread to the regional lymph nodes and one patient had distant metastases to the liver. There were no deaths. This study demonstrates that PSM is a distinctive, possible low-grade variant of melanoma usually lacking the histological features predictive of aggressive behaviour seen in ordinary melanoma. It should be managed in the same way as other melanomas with wide local excision.


Coherence resonances in an excitable thermochemical system with multiple stationary states.
A master equation approach is used to study the influence of internal fluctuations on the dynamics of three excitable thermochemical systems exhibiting continuous as well as discrete changes of temperature. The systems differ by the types of excitability. The dependences of the relative deviations from mean values of the interspike intervals and escape times from the stable stationary state on the size of the systems calculated from simulations of stochastic trajectories exhibit minima, which testify to the appearance of resonance phenomena. An explanation for the appearance of the stochastic resonances is presented.


Real-space pseudopotential method for computing the vibrational Stark effect.
The vibrational Stark shift is an important effect in determining the electrostatic environment for molecular or condensed matter systems. However, accurate ab initio calculations of the vibrational Stark effect are a technically demanding challenge. We make use of density functional theory constructed on a real-space grid to expedite the computation of this effect. Our format is especially advantageous for the investigation of small molecules in finite fields as cluster boundary conditions eliminate spurious supercell interactions and allow for charged systems, while convergence is controlled by a single parameter, the grid spacing. The Stark tuning rate is highly sensitive to the interaction between anharmonicity in a vibrational mode and the applied field. To ensure this subtle interaction is fully captured, we apply three parallel approaches: a direct finite field, a perturbative method, and a molecular dynamics method. We illustrate this method by applying it to several small molecules containing C-O and C-N bonds and show that a consistent result can be obtained.


Complex social housing reduces food neophobia in dairy calves.
Animals are often reluctant to consume novel feeds. Research suggests that social housing can reduce fearfulness in animals. The aim of this study was to test the prediction that social housing reduces food neophobia in dairy calves. Beginning immediately at birth, Holstein bull calves were either reared individually (n=18) or in a complex social group with other calves and cows (n=18). In food neophobia tests, calves were exposed to 2 identical buckets, one empty and the other filled with a novel food (chopped hay in trial 1 and chopped carrots in trial 2). Calves were tested for 30 min/d on 3 consecutive days starting at 70 d of age. Regardless of the type of food, socially housed calves consumed more of the novel feed compared with individually housed calves. In trial 1, intake of hay as fed averaged 35 ± 6 versus 18 ± 6 g/d for socially versus individually housed calves. In trial 2, intake of chopped carrots as fed averaged 27 ± 6 versus 6 ± 6 g/d for socially versus individually housed calves, respectively. Social rearing decreased the latency to eat the novel feed. Calves housed in a complex social group began eating the hay after 1:23 ± 1:13 versus 3:58 ± 1:10 min:s for individually housed calves. Latency to begin eating the chopped carrots averaged 3:09 ± 1:17 versus 6:38 ± 1:13 min:s for socially versus individually housed calves. Treatment had no effect on time spent eating, latency to approach the food bucket or the empty bucket in either trial, or on time spent manipulating the empty bucket. These results indicate that housing dairy calves in a complex social group reduces food neophobia. More generally, this study contributes to a series of studies showing that calves raised in more complex social environments may be better able to transition to other changes in their environment.


The DQ-HN[CACB] and DQ-HN(CO)[CACB] sequences with evolution of double quantum Calpha-Cbeta coherences.
The new variant of known HNCACB and HN(CO)CACB techniques is proposed that employs excitation and evolution of double quantum Calpha-Cbeta coherences. The most important features of the new method are: increased signal dispersion, lack of splittings due to 1J(Calpha-Cbeta) spin-spin couplings, and absence of accidental cancellations of positive and negative signals. The acquisition of both DQ-HN[CACB] and DQ-HN(CO)[CACB] techniques enables sequential assignment of protein backbone, using only Calpha-Cbeta DQ-frequencies. The determination of all Calpha and Cbeta chemical shifts requires, however, a comparison with HN(CO)CA or HNCA spectra. Examples of applications of the DQ-HN[CACB] and DQ-HN(CO)[CACB] experiments are presented, employing the 2D Reduced Dimensionality approach for 13C, 15N-labeled ubiquitin, and the 3D acquisition for 13C, 15N-double labeled Ca2+ -binding bovine S100A1 protein in the apo state (21 kDa) with overall correlation time of 8.1 ns.


Absolute Single Cavity Length Interrogation of Fiber-Optic Compound Fabry⁻Perot Pressure Sensors Through a White Light Non-Scanning Correlation Method.
A white light non-scanning correlation interrogation system was proposed and built to interrogate absolute length of the air cavity of fiber-optic compound Fabry⁻Perot pressure sensors for the extraction of pressure value. By carefully choosing thickness range and tilt angle of the optical wedge used for cavity length matching, correlation interferometric signal of the basal cavity can be naturally filtered out. Based on peak positioning by Fourier transform, bandpass filtering in frequency domain, inverse Fourier transform back to time domain, envelope fitting and zero fringe finding through a gravity center method, cavity length can be determined with an accuracy of 0.04%. The system was used for the interrogation of a fiber-optic compound Fabry⁻Perot pressure sensor under different pressures. For a pressure range of 0.1~2.9 Mpa, the linear relationship between the air cavity length and the gas pressure imposed was successfully extracted.


Specifying active components of educational interventions to promote adherence to treatment in glaucoma patients: application of a taxonomy of behavior change techniques.
In response to recent calls for clearer specification of behavior change interventions, the purpose of this study was to apply a system of taxonomy for behavior change techniques (BCTs) to two educational interventions to improve adherence to glaucoma eye drops. Clarification of constituent BCTs will promote easy and reliable application of the interventions in clinical settings and research. A published taxonomy of BCTs was used to code two interventions (group and individual) to increase adherence to eye drops. Intervention materials were coded by assigning a BCT label to each text unit. We noted the frequency with which each BCT occurred, compared the interventions in terms of the BCTs that were delivered, and identified whether the taxonomy was sufficient to describe the intervention components. The individual intervention consisted of 94 text units. Fifty-seven were identified as targeting behavior change and coded using 18 BCTs, many coded more than once. In the group intervention, 165 units of text were identified, and 125 were coded using 22 BCTs. The most frequently coded BCT was "provide information about behavior-health link" in the group intervention and "prompt barrier identification" in the individual intervention. The interventions included similar BCTs. All text units targeting behavior change were codable into BCTs. The similarity of the two interventions may have implications for the cost-effectiveness of the interventions. The taxonomy was found sufficient to describe both interventions. This level of specification can be used to ensure that precisely the same intervention that has been pilot tested is reproducible in the clinical setting and in any further research.


Antidiabetic activities of entagenic acid in type 2 diabetic db/db mice and L6 myotubes via AMPK/GLUT4 pathway.
Entada phaseoloides (L.) Merr., a traditional Chinese folk medicine, has been used in treating diabetes and other inflammatory disorders. Our previous study revealed that the triterpene saponins in E.Phaseoloides possessed an antidiabetic effect in type 2 diabetic rats by activating AMP-activated protein kinase (AMPK). Entagenic acid, the principal aglycon, isolated from the seed kernels of E. phaseoloides, has been proposed to possess a significant role in the antidiabetic effect, however, its actual effect and pertinent mechanisms are still unknown. The aim of the present study was to investigate the antidiabetic effect of entagenic acid in a type 2 diabetic animal model (C57BIKsj db/db mice) and its role in the regulation of glucose uptake in L6 myotubes, and to explore the possible molecular mechanisms. In vivo, average weekly body weight, daily water, food intake and postprandial blood glucose levels, the intraperitoneal insulin tolerance test, glucose tolerance test, serum lipid profiles and pancreatic histopathological changes in db/db mice treated with entagenic acid orally at different doses (5, 10 and 20mg/kg) were assessed and compared with wild-type littermates or vehicle- and metformin-treated db/db mice. In vitro, effects of entagenic acid on the glucose consumption and the phosphorylation of protein kinase B (AKT) and AMPK in L6 myotubes were evaluated. In vivo, entagenic acid significantly lowered postprandial blood glucose levels but not the body weight, normalized the serum lipid imbalance, improved the impaired glucose tolerance, insulin resistance, as well as the pathological changes in pancreatic islets. In vitro, entagenic acid dose-dependently promoted glucose utilization and enhanced the translocation and expression of glucose transporter 4 (GLUT4), and phosphorylation of AMPK but not AKT. The present study demonstrated that entagenic acid can markedly maintain the glucose homeostasis, improve insulin resistance and ameliorate dyslipidemia. Its antihyperglycemic effect could be caused by promoting AMPK mediated cellular signaling and GLUT4 translocation in muscles.


Molecular cloning of the full-length cDNA of (S)-hydroxynitrile lyase from Hevea brasiliensis. Functional expression in Escherichia coli and Saccharomyces cerevisiae and identification of an active site residue.
The full-length cDNA of (S)-hydroxynitrile lyase (Hnl) from leaves of Hevea brasiliensis (tropical rubber tree) was cloned by an immunoscreening and sequenced. Hnl from H. brasiliensis is involved in the biodegradation of cyanogenic glycosides and also catalyzes the stereospecific synthesis of aliphatic, aromatic, and heterocyclic cyanohydrins, which are important as precursors for pharmaceutical compounds. The open reading frame identified in a 1. 1-kilobase cDNA fragment codes for a protein of 257 amino acids with a predicted molecular mass of 29.2 kDa. The derived protein sequence is closely related to the (S)-hydroxynitrile lyase from Manihot esculenta (Cassava) and also shows significant homology to two proteins of Oryza sativa with as yet unknown enzymatic function. The H. brasiliensis protein was expressed in Escherichia coli and Saccharomyces cerevisiae and isolated in an active form from the respective soluble fractions. Replacement of cysteine 81 by serine drastically reduced activity of the heterologous enzyme, suggesting a role for this amino acid residue in the catalytic action of Hnl.


Cross-regulatory roles of interleukin (IL)-12 and IL-10 in atherosclerosis.
T cell cytokines are known to play a major role in determining protection and pathology in infectious disease. It has recently become clear that IL-12 is a key inducer of the type 1 T cell cytokine pattern characterized by production of IFN-gamma. Conversely, IL-10 down-regulates IL-12 production and type 1 cytokine responses. We have investigated whether IL-12 and IL-10 might be involved in a chronic inflammatory reaction, atherosclerosis. In atherosclerotic plaques, we found strong expression of IFN-gamma but not IL-4 mRNAs as compared to normal arteries. IL-12 p40 mRNA and IL-12 p70 protein were also found to be abundant in atherosclerotic plaques. IL-12 was induced in monocytes in vitro in response to highly oxidized LDL but not minimally modified LDL. The cross-regulatory role of IL-10 was indicated by the expression of IL-10 in some atherosclerotic lesions, and the demonstration that exogenous rIL-10 inhibited LDL-induced IL-12 release. These data suggest that the balance between IL-12 and IL-10 production contributes to the level of immune-mediated tissue injury in atherosclerotsis.