Clinical thermochemotherapy. A controlled trial in advanced cancer patients.
In vitro and in vivo animal studies and some clinical trials have shown apparent benefit from thermochemotherapy; however, this treatment modality has not been adequately tested in humans. This investigation evaluated response to and toxicity of secondary thermochemotherapy, using each patient as his own control. Patients with advanced cancer who had documented disease progression while receiving chemotherapy alone were subsequently treated with the same drug, by the same dose and route, combined with localized hyperthermia. Thirty-four patients whose diseases included metastatic colon carcinoma, melanoma, sarcoma and hepatoma in viscera (29) or surface tissues (5) were treated with combination thermochemotherapy for 1 hour daily for 5 days/month. Effective heating from 41 to 45 degrees C minimum tumor temperature was possible in 17/19 (89%) tumors in which temperatures could be measured safely. The authors observed 5 (15%) tumor regressions for 1 to 5 months (median, 2 months), and 19 (56%) tumor stabilizations (growth arrest of previously progressive disease) for 1 to 9 months (median, 4 months). Subjective improvement in activity and/or pain control occurred in 6 (18%) patients and 20 (59%) had no progression of symptoms during treatment. Moreover, there was no detectable morbidity from localized hyperthermia, and no evidence of increased chemotherapy toxicity. While the mechanism(s) of response is poorly understood, the documented disease regressions and stabilizations of previously progressive disease in 24 (71%) patients during secondary combination thermochemotherapy indicates that the addition of hyperthermia may have useful anticancer activity. Expanded trials are warranted.


[Property of liposomal fusion induced by acid-sensitive polymer].
The fusion between liposome-liposome, liposome-biomembarnes induced by acid-sensitive polymers has been systematically investigated. The polymer-liposomes were constructed by post-insertion method with the poly (2-ethylacrylic acid) (PEAA) alkylamide derivatives. The liposomal fusion was studied by use of fluorescence resonance energy transfer assay, particle size, fluorescent-photometer. The results indicated that the poly (2-ethylacrylic acid)-liposomes has very strong acidic induced fusion capability. Under acidic conditions, acid-sensitive polymer liposomes fused each other, the fusion closely related to the molecular weight of acid sensitivity polymer on the surface of liposomes. The acidic fusion of polymer-liposomes was dependent upon the lipids composition, the degree of fusion was reversely related to the cholesterol contents. Acid-en ci-nsitive polymer liposomes fused with erythrocyte ghosts. The liposomal fusion induced by acid-sensitive polymer associated with the increase of membrane permeability. The good acid-sensitivity of PEAA has been further demonstrated by membrane fusion in current experiments, and the liposomes prepared with lipid anchored-poly (2-ethylacrylic acid) were developeds s a potential pH sensitive delivery system.


[Ischemic preconditioning of the liver: from molecular bases to clinical application].
Ischemia-reperfusion injury is produced when an organ is deprived of blood flow (ischemia), which is then restored (reperfusion). In certain circumstances, this injury leads to irreversible organ damage. Several therapeutic strategies have been used to reduce the severity of this injury. One of these strategies is the application of brief and repetitive episodes of ischemia-reperfusion before prolonged ischemia-reperfusion (ischemic preconditioning). In the present article we review the molecular mechanisms through which ischemic preconditioning confers protection against ischemia-reperfusion injury. The application of ischemic preconditioning during liver surgery is discussed, both in normothermic situations such as liver resection and in situations of low temperature such as liver transplantation.


Trichophytum rubrum endonyx onychomycosis resistant to standard oral and topical therapies.
We present a 45 year-old man with an eight-year history of discoloration of the nail plate on his left hallux. He had been treated with two courses of oral terbinafine and topical 8% ciclopirox for presumed onychomycosis. On exam, his left great toenail contained a wide yellow-white longitudinal band involving a majority of the nail plate. No subungual debris, hyperkeratosis, or paronychial inflammation was present in the affected nail. Histopathology of the nail plate revealed numerous fungal elements arranged transversely and longitudinally, solely within the keratin layers of the nail plate; these were highlighted with periodic acid-Schiff (PAS) stain confirming endonyx onychomycosis. Cultures grew Trichophyton rubrum. All types of onychomycosis under the new classification system proposed by Hay et al. have now been associated with T. rubrum. Endonyx related to T. rubrum may be a particularly difficult infection to treat with oral or topical agents owing to the absence of robust local immune response and limited drug penetration to the interior nail plate. Physicians should be aware that this type of infection may require treatment with dual-agent therapy or alternative modalities including chemical or surgical plate avulsion or photodynamic therapy.


Need for cognition as a predictor of psychosocial identity development.
The authors examined the hypothesis that psychosocial identity development is related to need for cognition (NFC), a social-cognitive individual-difference variable defined as the desire to engage in effortful thinking (J. T. Cacioppo, R. E. Petty, J. Feinstein, & W. Jarvis, 1996). They administered 2 measures of psychosocial identity-a scale from the Extended Objective Measure of Ego Identity Status 2 (EOMEIS-2; G. R. Adams, L. Bennion, & K. Huh, 1989) and the Identity subscale of the Erikson Psychosocial Stage Inventory (EPSI; D. A. Rosenthal, R. M. Gurney, & S. M. Moore, 1981)-and the NFC scale to 200 incoming college students and approximately half of those students about 15 months later. Results indicate that people with higher psychosocial identity levels had higher NFC scores at both time periods. In addition, higher Time 1 NFC scores were related to higher Time 2 EOMEIS-2 achieved scores and lower Time 2 foreclosure and diffusion scores, and changes in NFC over the course of the study were positively correlated with EPSI changes and negatively correlated with changes in EOMEIS-2 foreclosure and diffusion scores. Results provide support for the importance of a cognitive and motivational individual-difference variable in the development of a unique and cohesive identity.


Comparison between midline and lateral fluid percussion injury in mice reveals prolonged but divergent cortical neuroinflammation.
Animal models are critical for determining the mechanisms mediating traumatic brain injury-induced (TBI) neuropathology. Fluid percussion injury (FPI) is a widely used model of brain injury typically applied either midline or parasagittally (lateral). Midline FPI induces a diffuse TBI, while lateral FPI induces both focal cortical injury (ipsilateral hemisphere) and diffuse injury (contralateral hemisphere). Nonetheless, discrete differences in neuroinflammation and neuropathology between these two versions of FPI remain unclear. The purpose of this study was to compare acute (4-72 h) and subacute (7 days) neuroinflammatory responses between midline and lateral FPI. Midline FPI resulted in longer righting reflex times than lateral FPI. At acute time points, the inflammatory responses to the two different injuries were similar. For instance, there was evidence of monocytes and cytokine mRNA expression in the brain with both injuries acutely. Midline FPI had the highest proportion of brain monocytes and highest IL-1β/TNFα mRNA expression 24 h later. NanoString nCounter analysis 7 days post-injury revealed robust and prolonged expression of inflammatory-related genes in the cortex after midline FPI compared to lateral FPI; however, Iba-1 cortical immunoreactivity was increased with lateral FPI. Thus, midline and lateral FPI caused similar cortical neuroinflammatory responses acutely and mRNA expression of inflammatory genes was detectable in the brain 7 days later. The primary divergence was that inflammatory gene expression was greater and more diverse subacutely after midline FPI. These results provide novel insight to variations between midline and lateral FPI, which may recapitulate unique temporal pathogenesis.


Alpha-amylase production by Bacillus subtilis CM3 in solid state fermentation using cassava fibrous residue.
In extraction of starch from cassava (Manihot esculenta Crantz), one of the major solid waste released is fibrous residues which constitute 15-20% by weight of the cassava chips/tuber processed. Production of alpha -amylase under solid state fermentation by Bacillus subtilis CM3 has been investigated using cassava fibrous residue. Response surface methodology (RSM) was used to evaluate the effect of the main variables, i.e. incubation period, initial medium pH, moisture holding capacity and temperature on enzyme production. A full factorial Central Composite Design (CCD) was applied to study these main factors that affected alpha -amylase production. The experimental results showed that the optimum incubation period, initial medium pH, moisture holding capacity and temperature were 6 days, 8.0, 70% and 50 degrees C, respectively.


Surface wetting and its effect on body and surface temperatures of domestic laying hens at different thermal conditions.
This study investigated the efficacy of surface wetting at different thermal conditions on core body, head, and dorsal surface temperatures in laying hens. Hens were sprinkled on the head and dorsal surface by releasing a sprinkling dosage of 10 mL.bird(-1). The first measurement was taken presprinkling, and the second was taken immediately postsprinkling and then repeated every 5 min for 20 min. The cooling water needs for intermittent partial surface wetting to relieve acute heat stress in the laying hens were quantified for 48 domestic laying hens under 4 experimental thermal conditions. The hens were kept at 4 thermal conditions at average dry-bulb temperatures of 31.30 +/- 0.03, 33.20 +/- 0.08, 36.01 +/- 0.12, and 40.24 +/- 0.08 degrees C; RH of 67.68 +/- 0.37, 51.78 +/- 1.98, 24.59 +/- 0.90, and 16.12 +/- 1.55%; and air velocities of 0.09 +/- 0.00, 0.07 +/- 0.00, 0.08 +/- 0.00, and 0.09 +/- 0.00 m.s(-1), respectively. The differences in core body, head, and dorsal surface temperatures among the 4 thermal groups were 0.15, 0.18, 0.23, and 0.22 degrees C for core body temperature; 1.63, 1.44, 2.51, and 0.97 degrees C for core head temperature; and 1.23, 1.37, 1.41, and 0.64 degrees C for core dorsal temperature at thermal conditions 1, 2, 3, and 4, respectively. There were significant differences in core body, head, and dorsal surface temperatures among the 4 thermal condition groups. It was concluded that the spraying interval was directly proportional to the product of the vapor pressure deficit and the thermal resistance of convective mass transfer of the wetted hens, because there were no significant differences in the air velocity among the 4 thermal condition groups and the air velocity was very low.


Isolation of Mycoplasmas from nasal swabs of calves affected with respiratory diseases and antimicrobial susceptibility of their isolates.
Nasal swabs of 293 calves were examined for Mycoplasma. The samples were collected from calves affected with respiratory diseases on 71 farms in various parts of Japan between 1996 and 1997. Mycoplasma bovirhinis was isolated from 47 of 293 calves (16.0%). Mycoplasma alkalescens, M. bovis, M. arginini, M. bovigenitalium and Acholeplasma spp. were isolated from 19 (6.5%), seven (2.4%), four (1.4%), four (1.4%) and 18 (6.1%) calves, respectively. Pasteurella multocida and P. haemolytica were isolated from 60% of Mycoplasma-positive calves. However, other bacteria were not isolated from calves. To evaluate the antimicrobial susceptibility of their isolates, 68 M. bovirhinis, 21 M. alkalescens and 10 M. bovis strains were examined for 12 antimicrobial agents. All isolates showed higher susceptibility to tiamulin than to the other drugs used in the study. However, erythromycin had no effect on any of the Mycoplasma strains studied. The field isolates were less susceptible than the type strains to some drugs, such as spiramycin, oxytetracycline and tylosin.


Quantum interference in macroscopic crystals of nonmetallic Bi2Se3.
Photoemission experiments have shown that Bi2Se3 is a topological insulator. By controlled doping, we have obtained crystals of Bi2Se3 with nonmetallic conduction. At low temperatures, we uncover a novel type of magnetofingerprint signal which involves the spin degrees of freedom. Given the mm-sized crystals, the observed amplitude is 200-500x larger than expected from universal conductance fluctuations. The results point to very long phase-breaking lengths in an unusual conductance channel in these nonmetallic samples. We discuss the nature of the in-gap conducting states and their relation to the topological surface states.


Magnetic Levitation Coupled with Portable Imaging and Analysis for Disease Diagnostics.
Currently, many clinical diagnostic procedures are complex, costly, inefficient, and inaccessible to a large population in the world. The requirements for specialized equipment and trained personnel require that many diagnostic tests be performed at remote, centralized clinical laboratories. Magnetic levitation is a simple yet powerful technique and can be applied to levitate cells, which are suspended in a paramagnetic solution and placed in a magnetic field, at a position determined by equilibrium between a magnetic force and a buoyancy force. Here, we present a versatile platform technology designed for point-of-care diagnostics which uses magnetic levitation coupled to microscopic imaging and automated analysis to determine the density distribution of a patient's cells as a useful diagnostic indicator. We present two platforms operating on this principle: (i) a smartphone-compatible version of the technology, where the built-in smartphone camera is used to image cells in the magnetic field and a smartphone application processes the images and to measures the density distribution of the cells and (ii) a self-contained version where a camera board is used to capture images and an embedded processing unit with attached thin-film-transistor (TFT) screen measures and displays the results. Demonstrated applications include: (i) measuring the altered distribution of a cell population with a disease phenotype compared to a healthy phenotype, which is applied to sickle cell disease diagnosis, and (ii) separation of different cell types based on their characteristic densities, which is applied to separate white blood cells from red blood cells for white blood cell cytometry. These applications, as well as future extensions of the essential density-based measurements enabled by this portable, user-friendly platform technology, will significantly enhance disease diagnostic capabilities at the point of care.


Fe-induced carbon nanotube/amorphous carbon polyhedral frame for superior potassium storage.
In todays energy field, the long-term development of lithium-ion batteries has been limited due to the scarcity and high cost of lithium resources. On the other hand, research towards of potassium-ion batteries (KIBs) is on the rise. Herein, we synthesize Fe-induced carbon nanotube/nitrogen-doped carbon (FNC) derived from metal-organic frameworks as a promising anode for KIBs. The carbon nanotubes can enhance the electronic conductivity and increase the contact area, thus improving the rate performance. Additionally, the amorphous carbon polyhedral frame can boost the electrochemical stability. Therefore, the FNC electrode exhibits a high reversible capacity (a charge capability of 268 mAh g-1 after 200 cycles at 0.1 A g-1) and an excellent rate performance.


Cancer resistance in transgenic mice expressing the SAC module of Par-4.
Prostate apoptosis response-4 (Par-4) is a tumor-suppressor protein that induces apoptosis in cancer cells, but not in normal/immortalized cells. The cancer-specific proapoptotic action of Par-4 is encoded in its centrally located SAC domain. We report here the characterization of a novel mouse model with ubiquitous expression of the SAC domain. Although SAC transgenic mice displayed normal development and life span, they were resistant to the growth of spontaneous, as well as oncogene-induced, autochthonous tumors. Resistance to tumorigenesis was linked to inhibition of nuclear factor-kappaB activity and induction of apoptosis by the SAC domain. Collectively, our findings provide genetic evidence that the SAC domain of Par-4 confers cancer resistance in transgenic mice without compromising normal viability or aging, and may have therapeutic significance.


Hypothetical biomolecular probe based on a genetic switch with tunable symmetry and stability.
Genetic switches are ubiquitous in nature, frequently associated with the control of cellular functions and developmental programs. In the realm of synthetic biology, it is of great interest to engineer genetic circuits that can change their mode of operation from monostable to bistable, or even to multistable, based on the experimental fine-tuning of readily accessible parameters. In order to successfully design robust, bistable synthetic circuits to be used as biomolecular probes, or understand modes of operation of such naturally occurring circuits, we must identify parameters that are key in determining their characteristics. Here, we analyze the bistability properties of a general, asymmetric genetic toggle switch based on a chemical-reaction kinetic description. By making appropriate approximations, we are able to reduce the system to two coupled differential equations. Their deterministic stability analysis and stochastic numerical simulations are in excellent agreement. Drawing upon this general framework, we develop a model of an experimentally realized asymmetric bistable genetic switch based on the LacI and TetR repressors. By varying the concentrations of two synthetic inducers, doxycycline and isopropyl β-D-1-thiogalactopyranoside, we predict that it will be possible to repeatedly fine-tune the mode of operation of this genetic switch from monostable to bistable, as well as the switching rates over many orders of magnitude, in an experimental setting. Furthermore, we find that the shape and size of the bistability region is closely connected with plasmid copy number. Based on our numerical calculations of the LacI-TetR asymmetric bistable switch phase diagram, we propose a generic work-flow for developing and applying biomolecular probes: Their initial state of operation should be specified by controlling inducer concentrations, and dilution due to cellular division would turn the probes into memory devices in which information could be preserved over multiple generations. Additionally, insights from our analysis of the LacI-TetR system suggest that this particular system is readily available to be employed in this kind of probe.


Exploring Students' Use of a Mobile Application to Support Their Self-Regulated Learning Processes.
Being able to self-regulate one's learning is essential for academic success but is also very difficult for students. Especially first year students can be overwhelmed with the high study load and autonomy in higher education. To face this challenge, students' monitoring and self-regulated learning (SRL) processes are crucial. Yet, often students are not aware of effective SRL strategies or how to use them. In this study, the use of a mobile application with gamification elements (i.e., Ace Your Self-Study App) to support first-year university students' SRL processes was investigated. In Study 1a, the Ace your self-study app was implemented in a first-year psychology course, and students' SRL skills, motivation, self-efficacy, app use and satisfaction, and performance were measured. The results showed a significant increase in autonomous motivation, controlled motivation, and metacognitive self-regulation skills (MSR-R) across the 5-week course. Moreover, students who used the mobile application with gamified elements showed higher autonomous motivation. Nevertheless, most students used the app only for a limited number of self-study sessions. In Study 1b, students' self-study experiences were captured using focus group interviews to shed some more light on why students did or did not use the app. The results show that if students feel they do not need support for their SRL processes during self-study, they are less inclined to use the app. Specifically, regarding using study strategies, it was found that only if students' strategies do not work well in their perception, they feel the need to change their way of studying and choose another strategy. These results are discussed in the context of theory on SRL and how to support it.


Serum calcium, phosphate and alkaline phosphate levels in epileptic children treated with phenobarbitone.
A longitudinal study to estimate the serum calcium, phosphate and alkaline phosphatase levels of 89 ambulatory epileptic children, aged between 3 years and 12 years, and having generalised tonic-clonic seizures, was carried out. None was on any form of medication for the treatment of seizures prior to presentation. Each patient received only phenobarbitone during the period of study. Serum levels of the biochemical parameters were determined at presentation, 6 months and 12 months, while serum phenobarbitone levels were estimated at 6 months and 12 months. Mean serum calcium, phosphate and alkaline phosphatase of the patients remained within the normal range. Using the paired 't' test, the differences in the levels of the parameters at the three measurements were not statistically significant (P > 0.05). Serum phenobarbitone levels remained within the therapeutic range during the period of study. Our results show that over a 12-month period, serum levels of calcium, phosphate, and alkaline phosphatase, remain normal in ambulant epileptic children treated with phenobarbitone.


Quantum dynamics of hydrogen atoms on graphene. II. Sticking.
Following our recent system-bath modeling of the interaction between a hydrogen atom and a graphene surface [Bonfanti et al., J. Chem. Phys. 143, 124703 (2015)], we present the results of converged quantum scattering calculations on the activated sticking dynamics. The focus of this study is the collinear scattering on a surface at zero temperature, which is treated with high-dimensional wavepacket propagations with the multi-configuration time-dependent Hartree method. At low collision energies, barrier-crossing dominates the sticking and any projectile that overcomes the barrier gets trapped in the chemisorption well. However, at high collision energies, energy transfer to the surface is a limiting factor, and fast H atoms hardly dissipate their excess energy and stick on the surface. As a consequence, the sticking coefficient is maximum (∼0.65) at an energy which is about one and half larger than the barrier height. Comparison of the results with classical and quasi-classical calculations shows that quantum fluctuations of the lattice play a primary role in the dynamics. A simple impulsive model describing the collision of a classical projectile with a quantum surface is developed which reproduces the quantum results remarkably well for all but the lowest energies, thereby capturing the essential physics of the activated sticking dynamics investigated.


p73 participates in WWOX-mediated apoptosis in leukemia cells.
The WWOX gene is considered to be a tumor-suppressor gene which encodes a protein (Wwox) implicated in various types of solid human cancers. It has been shown that overexpression of WWOX in human tumors promotes apoptosis in vitro and suppresses tumor growth in vivo. Recently, we investigated the effects of WWOX overexpression in vitro and observed marked growth arrest in human leukemia cells; however, the underlying mechanism(s) for this effect is unknown. The present study aimed to elucidate the primary mechanism(s) underlying WWOX-mediated apoptosis in human leukemia. We traced the interactions between WWOX and its associated factors p73 and p53 after WWOX overexpression was induced in Jurkat and K562 cells. Our data revealed that p73 participates in WWOX-mediated apoptosis in Jurkat and K562 cells through binding with Wwox in the cytoplasm without a nuclear-cytoplasmic translocation.


Loss of c-KIT expression in thyroid cancer cells.
Papillary thyroid carcinoma is the most frequent histologic type of thyroid tumor. Few studies investigated the role of c-KIT expression in thyroid tumors, suggesting a role for this receptor and its ligand in differentiation and growth control of thyroid epithelium and a receptor loss following malignant transformation. We investigated and correlated c-KIT expression levels and two known markers of thyrocytes differentiation, PAX8 and TTF-1, in malignant and benign cytological thyroid samples. Moreover, we performed functional studies on human papillary thyroid carcinoma cell line to associated c-KIT expression to thyrocytes differentiation and tumor proliferation. c-KIT and PAX8 expression resulted higher in benign samples compared to the malignant ones, and the expression levels of these two genes were significantly correlated to each other. We also observed that c-KIT overexpression led to an increase of PAX8 expression level together with a decrease of proliferation. Furthermore, c-KIT overexpressing cells showed a regression of typical morphological features of malignancy. Taken together these results suggest that c-KIT could be involved in the differentiation of thyroid cells and in tumor progression.


Human pancreatic secretion and intestinal motility: effects of ileal nutrient perfusion.
To study the effects of intraileal nutrients on human pancreatic secretion and gastrointestinal motility, nine healthy subjects were intubated with an oroileal multilumen tube for ileal perfusion, duodenal juice aspiration, and intestinal motility recording. The duodenum was perfused continuously with essential amino acids to induce submaximal stimulation of pancreatic enzyme secretion and fed motility pattern. Additional ileal perfusion with carbohydrate at quantities similar to those observed under physiological late postprandial conditions or fat at isocaloric loads significantly decreased pancreatic enzyme outputs by greater than 80% (P less than 0.001) compared with saline. Ileal carbohydrate or fat induced a duodenal motor activity front that migrated distally and was followed by reduced motility. In summary, ileal delivery of small quantities of nutrient markedly decreased endogenously stimulated pancreatic enzyme secretion in humans. This was associated with specific changes in fed intestinal motility that converted to patterns characteristic of the interdigestive state. Our findings suggest that the distal small intestine may participate in the late postprandial regulation of gastrointestinal function in humans.


In vitro and ex vivo enhancement of nonspecific phagocytosis by cefodizime.
The in vitro and ex vivo effects of cefodizime on some functional activities of both human neutrophils and monocytes were studied. In vitro experiments were performed with antibiotic concentrations ranging from 1 to 200 micrograms/ml. For the ex vivo study, 7 adult healthy controls were treated intravenously with 4 g/day of cefodizime for 6 days. We found that the drug modulated phagocytosis frequency and index when nonopsonized zymosan and heat-killed Candida albicans were used as phagocytic challenge both in vitro (from 25 micrograms/ml) and ex vivo 12 h after the last administration of cefodizime. No effect on the other phagocyte functional parameters was shown. The in vitro enhancement of nonspecific phagocytosis was demonstrated both in the presence of cefodizime and when phagocytes and particles were separately incubated with the drug.


Derivative domain fitting: a new method for resolving a mixture of normal distributions in the presence of a contaminating background.
Derivative domain least squares analysis is a new method for resolving multiple peaks superimposed on a slowly varying continuum into separate normal (Gaussian) distributions without developing a functional approximation for the continuum. The method is based on fitting the first derivative of the data with the first derivative of the sum of a series of normal distributions. A functional approximation for the continuum is not necessary as long as the first derivative of the continuum is approximately zero (i.e., the continuum varies slowly compared to the normal distributions).


Kinetic characteristics of transcriptional bursting in a complex gene model with cyclic promoter structure.
While transcription often occurs in a bursty manner, various possible regulations can lead to complex promoter patterns such as promoter cycles, giving rise to an important question: How do promoter kinetics shape transcriptional bursting kinetics? Here we introduce and analyze a general model of the promoter cycle consisting of multi-OFF states and multi-ON states, focusing on the effects of multi-ON mechanisms on transcriptional bursting kinetics. The derived analytical results indicate that burst size follows a mixed geometric distribution rather than a single geometric distribution assumed in previous studies, and ON and OFF times obey their own mixed exponential distributions. In addition, we find that the multi-ON mechanism can lead to bimodal burst-size distribution, antagonistic timing of ON and OFF, and diverse burst frequencies, each further contributing to cell-to-cell variability in the mRNA expression level. These results not only reveal essential features of transcriptional bursting kinetics patterns shaped by multi-state mechanisms but also can be used to the inferences of transcriptional bursting kinetics and promoter structure based on experimental data.


[Changes of TF and TFPI activities in patients with hypertension or coronary atherosclerotic heart disease].
To investigate the changes of tissue factor (TF) and tissue factor pathway inhibitor(TFPI) activities in patients with hypertension or coronary atherosclerotic heart (CAH) disease. TF activity was measured by two-stage assay, and TFPI activity was detected according to Sandset's method. Plasma TF activity in both patients with hypertension and patients with CAH disease was higher than that of normal control(P < 0.05). Hypercoagulative state may be involved in the pathogenetic processes of hypertension and CAH diseases. TF and TFPI activities have the likelihood to become the accessory diagnostic indexes for hypertension and CAH diseases.


Biomonitoring with wireless communications.
Wireless biomonitoring, first used in human beings for fetal heart-rate monitoring more than 30 years ago, has now become a technology for remote sensing of patients' activity, blood pulse pressure, oxygen saturation, internal pressures, orthopedic device loading, and gastrointestinal endoscopy. Technical advances in miniaturization and wireless communications have enabled development of monitoring devices that can be made available for general use by individuals/patients and caregivers. New methods for short-range wireless communications not encumbered by radio spectrum restrictions (e.g., ultra-wideband) will enable applications of wireless monitoring without interference in ambulatory subjects, in home care, and in hospitals.


Simultaneous quantitation of meperidine, normeperidine, tramadol, propoxyphene and norpropoxyphene in human plasma using solid-phase extraction and gas chromatography/mass spectrometry: Method validation and application to cardiovascular safety of therapeutic doses.
Several opioid analgesics have been related to the prolongation of cardiac repolarization, a condition which can be fatal. In order to establish a correct estimation of the risk/benefit balance of therapeutic doses of meperidine, normeperidine, tramadol, propoxyphene and norpropoxyphene, it was necessary to develop an analytical method to determinate plasma concentrations of these opioids. Here we describe a method which incorporates strong alkaline treatment to obtain norpropoxyphene amide followed by a one-elution step solid-phase extraction, and without further derivatization. Separation and quantification were achieved by gas chromatography/electron ionization mass spectrometry (GC/EI-MS) in selected-ion monitoring mode. Quantification was performed with 500 μL of plasma by the addition of deuterated analogues as internal standards. The proposed method has been validated in the linearity range of 25-1000 ng/mL for all the analytes, with correlation coefficients higher than 0.990. The lower limit of quantification was 25 ng/mL. The intra- and inter-day precision, calculated in terms of relative standard deviation, were 2.0-12.0% and 6.0-15.0%, respectively. The accuracy, in terms of relative error, was within a ± 10% interval. The absolute recovery and extraction efficiency ranged from 81.0 to 111.0% and 81.0 to 105.0%, respectively. A GC/MS method for the rapid and simultaneous determination of meperidine, normeperidine, tramadol, propoxyphene and norpropoxyphene in human plasma was developed, optimized and validated. This procedure was shown to be sensitive and specific using small specimen amounts, suitable for application in routine analysis for forensic purposes and therapeutic monitoring. To our knowledge, this is the first full validation of the simultaneous determination of these opioids and their metabolites in plasma samples.


Influence of vincristine on the Golgi complex of leukaemic lymphoblasts.
In vitro and in vivo effects of vincristine on the Golgi complex of leukaemic lymphoblasts were studied. The cells incubated in vitro for 4 hours with vincristine of 1.25 x 10(-5) M concentration lacked microtubules, but regularly contained paracrystals and parallel arrays of macrotubules associated with ribosomes. The Golgi complex in control lymphoblasts was represented by 1-3 dictyosomes (stacks of cisternae) grouped in one area. After exposure to vincristine the dictyosomes lay at a considerable distance from each other. In many of them the cisternae were shorter than in controls and distended or transformed into large vacuoles. In cells incubated in vitro with lower concentrations of vincristine (1.25 x 10(-6) and 1.25 x 10(-7) M) and in cells obtained after the second therapeutic dose of vincristine (in the course of normal clinical treatment) neither changes in the Golgi complex nor formation of paracrystals and macrotubules were observed.


β-Alanine ingestion increases muscle carnosine content and combat specific performance in soldiers.
The purpose of this study was to examine the effect of β-alanine (BA) ingestion on tissue carnosine levels and the impact such changes would have on combat specific activity. Eighteen soldiers (19.9 ± 0.8 year) from an elite combat unit were randomly assigned to either a BA or placebo (PL) group. Before and following a 30-day supplementation period carnosine content of the gastrocnemius muscle and brain was determined by proton magnetic resonance spectroscopy. During each testing session, participants performed military relevant tasks that included a 2.5 km run, a 1-min sprint, 50-m casualty carry, repeated 30-m sprints with target shooting, and a 2-min serial subtraction test (SST) to assess cognitive function under stressful conditions. A significant elevation (p = 0.048) in muscle carnosine content was noted in BA compared to PL. Changes in muscle carnosine content was correlated to changes in fatigue rate (r = 0.633, p = 0.06). No changes (p = 0.607) were observed in brain carnosine content. Following supplementation, no differences were noted in 2.5 km run, 1-min sprint, repeated sprint, or marksmanship performance, but participants in BA significantly (p = 0.044) improved their time for the 50-m casualty carry and increased their performance (p = 0.022) in the SST compared to PL. In summary, 30-days of BA ingestion can increase muscle carnosine content and improve aspects of military specific performance. Although cognitive performance was significantly greater in participants consuming BA compared to placebo, current study methods were unable to detect any change in brain carnosine levels, thus, the precise mechanism underlying these effects remains elusive.


Organic carbon storage in four ecosystem types in the karst region of southwestern China.
Karst ecosystems are important landscape types that cover about 12% of the world's land area. The role of karst ecosystems in the global carbon cycle remains unclear, due to the lack of an appropriate method for determining the thickness of the solum, a representative sampling of the soil and data of organic carbon stocks at the ecosystem level. The karst region in southwestern China is the largest in the world. In this study, we estimated biomass, soil quantity and ecosystem organic carbon stocks in four vegetation types typical of karst ecosystems in this region, shrub grasslands (SG), thorn shrubbery (TS), forest - shrub transition (FS) and secondary forest (F). The results showed that the biomass of SG, TS, FS, and F is 0.52, 0.85, 5.9 and 19.2 kg m(-2), respectively and the corresponding organic cabon storage is 0.26, 0.40, 2.83 and 9.09 kg m(-2), respectively. Nevertheless, soil quantity and corresponding organic carbon storage are very small in karst habitats. The quantity of fine earth overlaying the physical weathering zone of the carbonate rock of SG, TS, FS and F is 38.10, 99.24, 29.57 and 61.89 kg m(-2), respectively, while the corresponding organic carbon storage is only 3.34, 4.10, 2.37, 5.25 kg m(-2), respectively. As a whole, ecosystem organic carbon storage of SG, TS, FS, and F is 3.81, 4.72, 5.68 and 15.1 kg m(-2), respectively. These are very low levels compared to other ecosystems in non-karst areas. With the restoration of degraded vegetation, karst ecosystems in southwestern China may play active roles in mitigating the increasing CO2 concentration in the atmosphere.


[Clinical features of respiratory infections due to influenza virus in hospitalized children].
Infants and toddlers have the highest influenza hospitalization rate in pediatrics. Although the impact of this virus in children has been recognized, there is no defined statement related to vaccination in this population. To describe clinical and epidemiological characteristics of complicated influenza infections in hospitalized children. All hospitalizations due to influenza virus were recorded prospectively between March and June 2004. We registered 40 laboratory-confirmed influenza admissions. Median age was 24 months (range: 15 days-14.5 years), 52% males, 18 younger than 2 years. Most of them had an underlying medical condition. The most common conditions were recurrent wheeze in 17, a neurological disease in 7 and asthma in 6. Twenty had more than one condition and 15 were previously healthy. The average days of respiratory symptoms and fever prior to admission were 5 and 3, respectively. The most common discharge diagnoses were concomitant viral-bacterial pneumonia in 53%, viral pneumonia in 38% and laryngitis in 8%. Influenza virus A was identified in 34/40 children. Oxygen supplementation was required by 34 cases; 20% of which required an O2 inspired fraction over 40%. The average days of hospitalization and oxygen were 4 and 3, respectively. Eleven children were treated with amantadine and 21 with antimicrobials. Four children were admitted to pediatric intensive care units and two cases required non-invasive ventilatory support. No deaths were recorded. Our data confirms the importance of influenza virus infection in children, as measured by admission rates, complications and length of hospital stay. Young children are a risk group for which immunization is recognized as protective.


[Context and background after infarction. GISSI nursing].
While the clinical course of myocardial infarction (AMI) from symptoms to outcome has been investigated in great detail, only a few data are available from the patients' side on their subjective feelings, their experience and their awareness of risk before the occurrence of AMI. A sample population of 3863 AMI patients, randomized for the GISSI-3 study, was interviewed by nurses an average of four days after the AMI. The questions explored the activities performed at the time the AMI occurred, the patients' perceptions and the preventive practices that were adopted. AMI occurs in "normal" life situations: only 10.3% patients reported heavy exertion immediately before the onset of AMI and 5.6% reported emotional involvement as a possible acute trigger. A large majority of patients would associate the AMI with something wrong or unusual occurring before the event. On average, > 60% patients associated the AMI with cardiac symptoms (chest pain, shortness of breath) or with psychological symptoms, such as anxiety; an important minority (30%) associated it with joint pain or a fever, suggesting inflammation as a possible trigger event. Preventive practices were declared by 25% of patients, but the number drops to 6% if at-risk patients (those with a history of AMI or angina) are excluded. Diet and drugs are the most widely adopted practices. Male sex and a history of AMI are linked with a more widespread use of preventive practices. Younger patients and patients with a higher education modified their lifestyle (exercise, smoke) to a greater extent, while there are no major differences between patients with or without a history of hypertension and angina. Large-scale use of preventive practices is very unlikely, and this is true not only for the general population, but also for AMI "at-risk" groups. These patients (elderly, less-educated people) should be the target of specific educational interventions aimed at increasing the awareness of risk and promoting safer and more health-oriented lifestyles.


Genetic susceptibility to post-endoscopic retrograde cholangiopancreatography pancreatitis identified in propensity score-matched analysis.
A previous history of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is a risk factor for PEP, suggesting that there may be a genetic predisposition to PEP. However, nothing is known about this yet. The aim of this study was to identify genetic variations associated with PEP. A cohort of high-risk PEP patients was queried from December 2016 to January 2019. For each PEP case, two propensity score-matched controls were selected. Whole exome sequencing was performed using blood samples. Genetic variants reported to be related to pancreatitis were identified. To discover genetic variants that predispose to PEP, a logistic regression analysis with clinical adjustment was performed. Gene-wise analyses were also conducted. Totals of 25 PEP patients and 50 matched controls were enrolled. Among the genetic variants reported to be associated with pancreatitis, only CASR rs1042636 was identified, and it showed no significant difference between the case and control groups. A total of 54,269 non-synonymous variants from 14,313 genes was identified. Logistic regression analysis of these variants showed that the IRF2BP1 rs60158447 GC genotype was significantly associated with the occurrence of PEP (odds ratio 2.248, FDR q value = 0.005). Gene-wise analyses did not show any significant results. This study found that the IRF2BP1 gene variant was significantly associated with PEP. This genetic variant is a highly targeted PEP risk factor candidate and can be used for screening high-risk PEP groups before ERCP through future validation. (ClinicalTrials.gov no. NCT02928718).


Lymphocyte functional antigens stabilize agglutination between Reed-Sternberg cells and T cells, but are not responsible for homotypic binding of Hodgkin's Reed-Sternberg cells.
The neoplastic (Hodgkin's Reed-Sternberg [H-RS]) cells in Hodgkin's disease (HD) are known for their unique capacity to form rosettes with unprimed T cells. Recently, a family of leukocyte-adherence molecules (LFA-1 and LFA-2) has been identified on T lymphocytes. The molecules bind to intercellular-adhesion molecules (ICAMs) and to LFA-3, respectively, which are associated with antigen-presenting cells. In this study, the authors examined whether these molecules are responsible for the homotypic and heterotypic agglutination that occurs in the cultured H-RS cells HDLM-1, HDLM-1d, and KM-H2. Despite their similar expressions of LFA-3 and ICAM-1, the different H-RS cells tested showed different growth patterns in culture. HDLM-1 cells grew singly, whereas HDLM-1d and KM-H2 cells grew in clumps. The HDLM-1 cells formed clumps when mixed with peripheral-blood T lymphocytes, cells of two lymphoblastic T-cell lines (MOLT-3 and MOLT-4), and cells of two monocyte lines (ML-1 and U-937). The addition of anti-LFA and ICAM-1 antibodies to cultures did not result in disassembly of the homotypic clusters of HDLM-1d or KM-H2 cells and it did not cause any significant changes in the size of heterotypic clusters or in the timing of cluster formation of HDLM-1 cells with other types of cells. In all studies, the cell clusters formed during homotypic and heterotypic aggregation were disassembled only minimally by cell shearing with pipetting. The disaggregation by pipetting was slightly more prominent in the presence of antibodies than was that of control cultures. However, in no case did the use of monoclonal antibodies (MAbs) and cell shearing cause complete disaggregation of homotypic and heterotypic clusters. The result seems to suggest that binding between H-RS cells and T cells and between H-RS cells and monocytes is not mediated primarily by LFAs and ICAMs, but that the binding may be strengthened in the presence of these molecules.


Cementation of a dual-mobility cup into a well-fixed cementless shell in patients with high risk of dislocation undergoing revision total hip arthroplasty.
Cementation of polyethylene liners into well-fixed cementless metal shells has become an option during revision total hip arthroplasty (THA). We report the results of cementing a dual-mobility (DM) component into a stable acetabular shell in high-risk patients undergoing revision THA. A single-centre series of 10 patients undergoing revision THA with a DM cup cemented into an existing well-fixed shell between 2012 and 2016 were retrospectively reviewed. Failure due to aseptic loosening or instability and implant survival at last follow-up were analysed. The average age was 79.2 years and mean follow-up was 3.5 years. Indications were recurrent hip dislocation in 8 cases and intraoperative instability with moderate abductor insufficiency in 2 cases. In cases with recurrent dislocation, the aetiology of instability was classified by Wera type. At the latest follow-up, Harris Hip Scores had improved from 49.3 preoperatively to 71.3 postoperatively (p = 0.098). In the 8 patients with recurrent dislocation, 4 cases (50%) had an unclear aetiology (Wera type 6), 2 (25%) abductor deficiency (Wera type 3) and 2 (25%) late polyethylene wear (type 5).Postoperative recurrent dislocation occurred in 1 hip (10%). No cases of intraprosthetic dislocation, aseptic loosening of the previous shell or dissociation at the cement-cup interface were identified. Although the follow-up of this series is short, cementation of a DM cup into a previous well-fixed socket seems to be a viable option to treat and prevent instability after revision THA, without providing constraint at the cement-cup interface.


Ruptured abdominal aortic aneurysms: endovascular repair versus open surgery--systematic review.
To perform a systematic review of studies in which endovascular repair was compared with open surgery in the treatment of patients with a ruptured abdominal aortic aneurysm (AAA). A search of the English-language literature from January 1994 until March 2006 was performed. Inclusion criteria for studies were that they were about a comparison between patients who underwent endovascular repair and patients who underwent open surgery, that each treatment group included at least five patients, that information about patients' hemodynamic condition at presentation was reported, and that 30-day mortality was reported for each treatment group. Two reviewers independently extracted the data, and discrepancies were resolved by an arbiter. Random-effects models and meta-regression analysis were used to calculate crude and adjusted odds ratios (ORs) for endovascular repair versus open surgery. Ten studies, in which the results of 478 procedures (n=148 for endovascular repair, n=330 for open surgery) were reported, met the inclusion criteria. All studies were observational; no randomized controlled trials were found. The pooled 30-day mortality was 22% (95% confidence interval [CI]: 16%, 29%) for endovascular repair and 38% (95% CI: 32%, 45%) for open surgery. The pooled rate for total systemic complications was 28% (95% CI: 17%, 48%) for endovascular repair and 56% (95% CI: 37%, 85%) for open surgery. The crude OR for 30-day mortality for endovascular repair compared with open surgery was 0.45 (95% CI: 0.28, 0.72). After adjustment for patients' hemodynamic condition, the OR was 0.67 (95% CI: 0.31, 1.44). In this systematic review, after adjustment for patients' hemodynamic condition at presentation, a benefit in 30-day mortality for endovascular repair compared with open surgery for patients with a ruptured AAA was observed, but it was not statistically significant.


Long noncoding RNAs contribute to DNA damage resistance in Arabidopsis thaliana.
Efficient repair of DNA lesions is essential for the faithful transmission of genetic information between somatic cells and for genome integrity across generations. Plants have multiple, partially redundant, and overlapping DNA repair pathways, probably due to the less constricted germline and the inevitable exposure to light including higher energy wavelengths. Many proteins involved in DNA repair and their mode of actions are well described. In contrast, a role for DNA damage-associated RNA components, evident from many other organisms, is less well understood. Here, we have challenged young Arabidopsis thaliana plants with two different types of genotoxic stress and performed de novo assembly and transcriptome analysis. We identified three long noncoding RNAs (lncRNAs) that are lowly or not expressed under regular conditions but up-regulated or induced by DNA damage. We generated CRISPR/Cas deletion mutants and found that the absence of the lncRNAs impairs the recovery capacity of the plants from genotoxic stress. The genetic loci are highly conserved among world-wide distributed Arabidopsis accessions and within related species in the Brassicaceae group. Together, these results suggest that the lncRNAs have a conserved function in connection with DNA damage and provide a basis for mechanistic analysis of their role.


Structural and functional abnormalities in migraine patients without aura.
Migraine is a primary headache disorder characterized by recurrent attacks of throbbing pain associated with neurological, gastrointestinal and autonomic symptoms. Previous studies have detected structural deficits and functional impairments in migraine patients. However, researchers have failed to investigate the functional connectivity alterations of regions with structural deficits during the resting state. Twenty-one migraine patients without aura and 21 age- and gender-matched healthy controls participated in our study. Voxel-based morphometric (VBM) analysis and functional connectivity were employed to investigate the abnormal structural and resting-state properties, respectively, in migraine patients without aura. Relative to healthy comparison subjects, migraine patients showed significantly decreased gray matter volume in five brain regions: the left medial prefrontal cortex (MPFC), dorsal anterior cingulate cortex (dACC), right occipital lobe, cerebellum and brainstem. The gray matter volume of the dACC was correlated with the duration of disease in migraine patients, and thus we chose this region as the seeding area for resting-state analysis. We found that migraine patients showed increased functional connectivity between several regions and the left dACC, i.e. the bilateral middle temporal lobe, orbitofrontal cortex (OFC) and left dorsolateral prefrontal cortex (DLPFC). Furthermore, the functional connectivity between the dACC and two regions (i.e. DLPFC and OFC) was correlated with the duration of disease in migraine patients. We suggest that frequent nociceptive input has modified the structural and functional patterns of the frontal cortex, and these changes may explain the functional impairments in migraine patients.


Octogenarians undergoing combined aortic valve replacement and myocardial revascularization: perioperative mortality and medium-term survival.
Aim of the study was to answer the question whether the mortality and morbidity of octogenarians undergoing combined aortic valve replacement and myocardial revascularization (AVR + CABG) is higher than that of younger patients. Between 01/1995 and 12/2002, 242 patients underwent AVR + CABG in our institution. 37 patients were older than 80 years (16 male, 21 female, median pressure gradient over the aortic valve: 53 mmHg, median EF: 62%), 205 patients were younger than 80 years (133 male, 72 female, median gradient 48 mmHg, median EF: 61%). NYHA class, aortic valve area and valve calcification were worse in the 80+ group. Biological valve prostheses were implanted in 94.6% of the older and in 45.4% of the younger patients (p < 0.001). Perioperative complications occurred more often (p = 0.0188) in the 80+ group (86.5% experienced 1 or more complications) than in the 80- group (66.3%). Similarly, the MACE (Major Adverse Cardiovascular Events) rate was higher (p = 0.0448) in the 80+ group than in the 80- group. Bleeding occurred (p = 0.092) more often in younger (9.3%) than in older (0%) patients, while renal insufficiency was more frequent (p = 0.0164) in older (21.6%) than in younger patients (7.8 %). The 30-day mortality was higher (p = 0.0045) in older (21.6%) than in younger patients (5.8%). Multivariate analysis revealed an odds ratio for early death of 2.9 (CI 1.014-8.397) for patients older than 80 years. The late death rate within the first 5 years after surgery was comparable in both groups (80- group 24.4%, 80+ group 24.3%). Postoperative quality of life was significantly worse in the 80+ group in 4 out of 8 functions. Octogenarians undergoing AVR + CABG have a relatively high perioperative complication rate and mortality, but show a stable medium-term survival. The perioperative complication rate is higher in older than in younger patients, and the postoperative quality of life with regard to bodily functions is acceptable but significantly worse than that of younger patients.


Molecules in motion: chemical reaction and allied dynamics in solution and elsewhere.
After my acceptance of the kind invitation from Todd Martínez and Mark Johnson, Co-Editors of this journal, to write this article, I had to decide just how to actually do this, given the existence of a fairly personal and extended autobiographical account of recent vintage detailing my youth, education, and assorted experiences and activities at the University of Colorado, Boulder, and later also at Ecole Normale Supérieure in Paris ( 1 ). In the end, I settled on a differently styled recounting of the adventures with my students, postdocs, collaborators, and colleagues in trying to unravel, comprehend, describe, and occasionally even predict the manifestations and consequences of the myriad assortment of molecular dances that contribute to and govern the rates and mechanisms of chemical reactions in solution (and elsewhere). The result follows.


[The Kibbutz physician: family medicine theory in practice].
124 of 251 physicians living and working in 109 of the 194 kibbutzim in Israel answered a 125-item postal questionnaire on their professional and personal characteristics and the special issues affecting a kibbutz physician. Most were specialists in family practice, had had the best of modern medical training, were deeply involved in their communities, and were familiar with all aspects of their patients' lives. They were given the opportunity to express the bio-psycho-social model of family medicine. This study relates to the special encounter of family medicine theory and its practice in the kibbutz system of health care delivery, including the problems of the kibbutz physician and the degree of personal satisfaction derived.


New studies of post-Pleistocene human skeletal remains from the Rift Valley, Kenya.
Prehistoric human crania from Bromhead's Site, Willey's Kopje, Makalia Burial Site, Nakuru, and other localities in the Eastern Rift Valley of Kenya are reassessed using measurements and a multivariate statistical approach. Materials available for comparison include series of Bushman and Hottentot crania. South and East African Negroes, and Egyptians. Up to 34 cranial measurements taken on these series are utilized to construct three multiple discriminant frameworks, each of which can assign modern individuals to a correct group with considerable accuracy. When the prehistoric crania are classified with the help of these discriminants, results indicate that several of the skulls are best grouped with modern Negroes. This is especially clear in the case of individuals from Bromhead's Site, Willey's Kopje, and Nakuru, and the evidence hardly suggests post-Pleistocene domination of the Rift and surrounding territory by "Mediterranean" Caucasoids, as has been claimed. Recent linguistic and archaeological findings are also reviewed, and these seem to support application of the term Nilotic Negro to the early Rift populations.


[Significance of monitoring pulmonary arterial pressure and cardiac function in neonates with pulmonary or extra-pulmonary acute respiratory distress syndrome].
To evaluate the dynamic changes of pulmonary arterial pressure (PAP) and cardiac function in neonates with pulmonary or extra-pulmonary acute respiratory distress syndrome (ARDSp/ARDSexp). An observational study was conducted. A total of 128 neonates with ARDS admitted to neonatology department of the Affiliated Yancheng Hospital of Southeast University Medical College from January 2016 to December 2020 were enrolled, with 67 neonates in ARDSp group and 61 neonates in ARDSexp group. After starting mechanical ventilation, oxygenation index [OI, OI = mean airway pressure (Pmean)×fraction of inspired oxygen (FiO2)/arterial partial pressure of oxygen (PaO2)×100], PAP, cardiac function parameters [cardiac index (CI), left ventricular ejection fraction (LVEF), right ventricular Tei (RV-Tei)], and plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) were compared between the two groups; the incidence of pulmonary arterial hypertension [PAH, pulmonary artery systolic pressure (PASP) was more than 35 mmHg (1 mmHg = 0.133 kPa) or more than 2/3 of the systolic blood pressure of the body circulation] of neonates was recorded. The correlation between PAP and NT-proBNP was analyzed by Pearson correlation method. The dynamically changes in PAP and RV-Tei before and after using Milrinone in neonates with ARDSp and ARDSexp combined with moderate-severe PAH (PASP 50-69 mmHg was moderate, and PASP ≥ 70 mmHg was severe) were observed. The duration of mechanical ventilation, total length of hospital stay and prognosis were recorded; Kaplan-Meier survival curve was drawn to analyze the 28-day survival of the two groups. The occurrence rate of PAH in ARDSp group was significantly higher than that in ARDSexp group (97.01% vs. 70.49%, P < 0.01). OI, PAP, NT-proBNP and RV-Tei were also higher [OI: 17.61±6.12 vs. 11.04±5.35, PAP (mmHg): 64.27±9.54 vs. 53.61±6.47, NT-proBNP (ng/L): 23 126.32±1 485.14 vs. 18 624.24±1 647.15, RV-Tei: 0.61±0.22 vs. 0.52±0.19, all P < 0.05], but there was no significant difference in CI or LVEF between the two groups. Pearson correlation analysis showed that PAP was significantly positively correlated with NT-proBNP (r = 0.918, P < 0.01). There were 97 ARDS neonates with moderate-severe PAH with 63 in ARDSp group and 34 in ARDSexp group. Both PAP and RV-Tei in the two group showed a decreasing trend with the prolongation of Milrinone treatment, the decrease was more significant in the ARDSexp group compared with ARDSp group, the difference was statistically significant at 72 hours of treatment [PAP (mmHg): 38.42±8.95 vs. 45.67±13.32, RV-Tei: 0.58±0.19 vs. 0.61±0.13, both P < 0.05]; there was no significant difference in PAP or RV-Tei before extubation between the two groups. The duration of mechanical ventilation and the total length of hospital stay in ARDSp group were significantly longer than those in ARDSexp group [duration of mechanical ventilation (days): 10.12±1.36 vs. 6.31±1.31, total length of hospital stay (days): 16.52±3.25 vs. 13.12±3.57, both P < 0.01]. Kaplan-Meier survival curve showed that neonate in ARDSp group had a significantly lower 28-day cumulative survival rate as compared with ARDSexp group (82.09% vs. 95.01%; Log-Rank test: χ2 = 5.062, P = 0.025). Both PAP and RV-Tei were significantly increased in neonates with ARDS, PAP in neonates with ARDSp were significantly higher than that in neonates with ARDSexp. Dynamic monitoring of PAP and RV-Tei can reflect the severity of ARDS in neonates, and targeted intervention of pulmonary surfactant combined with Milinone for improving oxygenation and reducing PAP is one of the effective methods for the treatment of PAH.


Structural determinants of the selectivity of KTS-disintegrins for the alpha1beta1 integrin.
KTS-disintegrins are a subfamily of short monomeric disintegrins that are potent and selective inhibitors of alpha1beta1 integrin. The amino acid sequence of the new KTS-disintegrin, viperistatin, differs from previously characterized obtustatin in three residues at position 24 (within the integrin binding loop), 38 (hydrophobic core) and 40 (C-terminal region). Noteworthy, viperistatin is about 25-fold more potent than obtustatin inhibiting the binding of this integrin to collagen IV. Synthetic peptides representing the full-length of integrin-binding loops of these disintegrins showed that the Leu24/Arg substitution appears to be partly responsible for the increased inhibitory activity of viperistatin over obtustatin.


Aromatase inhibitors and inactivators for breast cancer therapy.
Aromatase inhibitors and inactivators are increasingly important to the therapy of advanced breast cancer in postmenopausal women. These compounds are also currently being evaluated in the adjuvant setting and may have potential in breast cancer prevention. In addition to the recent clinical results, experimental research with development of aromatase 'knockout' mice as well as certain clinical observations in individuals lacking this enzyme have deepened our understanding of estrogens outside of the field of reproduction. Such information should help us to further develop this type of therapy in breast cancer and, in particular, extend our understanding of the lack of complete cross-resistance between aromatase inhibitors and inactivators. Clinically, third-generation aromatase inhibitors and inactivators have shown superiority compared with conventional treatment in advanced postmenopausal breast cancer with respect to second-line (tamoxifen failures) as well as first-line therapy. The fact that tamoxifen is noncurative in metastatic disease but improves long-term survival in the adjuvant setting suggests that even modest improvements in therapy of advanced disease may be translated into survival benefits in patients with early disease. In addition, these novel compounds with lack of complete cross-resistance extend the scope of using sequential treatment options to maximise the duration of optimal endocrine therapy in metastatic breast cancer disease.


Case report on the radiographic features of epipericardial fat necrosis in a patient presenting with acute chest pain.
Epipericardial fat necrosis (EFN) is a rare and benign condition. The three cardinal features of EFN are acute pleuritic chest pain, radiological features of an encapsulated fatty lesion within the epipericardial fat and the presence of inflammation within the surrounding pericardium. The exact aetiology is still unknown, and there are no known risk factors. The condition appears to be a transient process with no associated long-term complications. In this case study, we demonstrate the multitude of radiological features associated with this condition. A 29-year-old Caucasian female presented with acute pleuritic chest pain. There were no acute changes on her blood work, electrocardiogram (ECG) or echocardiogram. The chest radiograph showed an opacity projected within the anterior mediastinum. Further imaging, with computed tomography (CT) chest with contrast, was performed to define the characteristics of the opacity. This confirmed an encapsulated, mixed fat, soft tissue density in the left pericardiac region deemed to represent EFN. Follow-up magnetic resonance (MR) cardiac imaging at 1, 4 and 12 months demonstrated the self-resolving characteristics of this condition. EFN is a rare differential diagnosis to consider in patients presenting with acute pleuritic chest pain when laboratory tests are normal and there are no acute ECG findings. EFN should be excluded by imaging with CT or MRI of the heart. We have demonstrated through follow-up MR imaging the progression and resolution of EFN over 12 months.


A multi-orientation low-frequency rotational accelerometer.
We present a low frequency rotational accelerometer coined ALFRA with a few nrad/Hz readout sensitivity above 20 mHz and 0.1 nrad/Hz above 50 mHz. The ALFRA is a beam-balance style rotation sensor, which pivots about a cross flexure designed to allow mounting with any orientation, the axis of the pivot determining which rotational component is measured. The high sensitivity is achieved through the use of a walk-off sensor readout used in a feedback loop with an electromagnetic coil to keep the beam dynamically locked. The ALFRA is relatively compact for a ground rotation sensor, measuring at 780 × 240 × 55 mm3.


Evans blue as counterstain in the demonstration of muscle antibodies by immunofluorescence in myasthenia gravis.
The binding of muscle antibodies to skeletal muscle was studied by immunofluorescence techniques. The non-specific fluorescence was not significantly reduced by absorption of the conjugate by tissue powder but was abolished by counterstaining with a 0.1% Evans blue. Possible explanations for this effect are discussed. By this method, immunofluorescence may become more useful in the demonstration of muscle antibodies.


Ordering transitions of semifluorinated diblock copolymers.
A series of diblock copolymers consisting of a hydrophilic polyethylene oxide (PEO) and a hydrophobic poly(1H,1H-dihydroperfluorooctyl methacrylate) (PDHFOMA) block were synthesized with different chain lengths for application to self-assembled nanopatterning structures. The morphology of poly(DHFOMA5k-b-EO5k), poly(DHFOMA10k-b-EO10k), and poly(DHFOMA20k-b-EO20k) spin cast from micellar solution in chloroform at room temperature were spherical with average diameter of 12 nm, 17 nm and 26 nm, respectively by TEM analysis. The spherical structures were reorganized to different shapes with thermodynamically stable morphologies upon annealing above glass transition temperature (Tg). PDHFOMA block domains changed to well ordered cylindrical domains, inversed continuous phase, and large composite spherical domains for 5 k, 10 k, and 20 k block copolymer, respectively.


Utilization and Associated Factors of Insecticide Treated Bed Net among Pregnant Women Attending Antenatal Clinic of Addis Zemen Hospital, North-Western Ethiopia: An Institutional Based Study.
Insecticide treated bed net (ITN) is one type of cost-effective vector control approach for the prevention of malaria. It has to be treated with insecticide and needs ongoing treatment with chemicals. Malaria infcetion during pregnancy is a amajor health problem in Ethiopia. Little is known about the utilization of ITN by pregnant women in the study area. This study was aimed to assess utilization and associated factors of insecticide-treated nets among pregnant women in Adis Zemen Hospital. This hospital based cross-sectional study was conducted in Adis Zemen from May 1 to 30, 2018, among 226 pregnant mothers. After obtaining informed consent, data were collected using a pretested structured questionnaire via face to face interview. To reach the study unit, a systematic random sampling technique was used. The collected data were entered, cleaned, checked using Epi data version 3.1, and finally analyzed using SPSS version 20. Binary and multivariable logistic regressions were computed to identify significantly associated variables at 95% confidence interval. A total of 226 pregnant mothers attending antenatal clinics participated in making the response rate 100%. Among a total 226 subjects, 160(70.8%) of mothers had good utilization of insecticide bet net. Mothers who had an educational status of college and above were 2.8 times more likely to utilize insecticide-treated bed net than mothers who could not read and write (AOR; 2. 8: CI; 1.9, 6.5). Mothers whose age was >30 were 70% times less likely utilized insecticide-treated bed net than mothers whose age was 30 and less (AOR;.3: CI;.2,.6). Utilization of insecticide-treated bed net by pregnant women is low in the study area. The participants' age, educational status, household monthly income, and husband educational status were significantly associated with utilization of insecticide-treated bed net. Different stakeholders shall give a special attention to awareness creation on advantageous of insecticide bed net.


How to arouse students' desire to learn biochemistry.
Teaching biochemistry well is not an easy job for teachers and so is learning biochemistry well for students. Just as many students often complain, they virtually always fail in either physiology or biochemistry. I have been teaching biochemistry at Nanjing University for over 25 years and am very successful in my biochemistry-teaching career. The way and style that I teach biochemistry is highly praised by both my students and my fellow teachers. As an instructor, the most important thing is, I think, you have to do your best to arouse or ignite students' interest in biochemistry learning. But how? In this article, I will introduce many first-hand practical tips on how to arouse the students 'interest in studying biochemistry from giving the first lecture to last lecture, from how to combine advanced teaching methods with traditional teaching methods to how to combine classic biochemistry with latest biochemical developments, from the main classroom teaching to organization of extracurricular activities as the second classroom, and so on. These tips are proven very useful and then can be followed by other professors who are teaching biochemistry. Hopefully, they can help many professors improve their skills for teaching biochemistry.


[Role of cyclic 3',5'-adenosine monophosphate in the development of Salmonella infection in an experiment].
The changes in cAMP levels in spleen macrophages of mice infected with low-virulent and virulent Salmonella strains and the effect of propranolol on Salmonella reproduction in the spleen, and the outcome of Salmonella-induced infection have been studied. A persistent increase in cAMP levels in spleen macrophages during Salmonella infection caused by virulent Salmonella strains has been demonstrated. Low-virulent Salmonella strains failed to cause the elevation of cAMP levels in spleen macrophages. Propranolol injection to mice prevented intensive Salmonella reproduction in the spleen and diminished the animal mortality rate.


JAK INHIBITOR CLINICAL RESPONSE IN POLYARTHRITIS: CASE REPORT.
The heterogeneity of rheumatoid arthritis (RA) presentation and molecular signature of RA subclasses in patients with early changes of small peripheral joints still remains a challenging problem. In clinical setting, classification of the disease subtypes is not possible and treatment adjustment is based on the continuous Disease Activity Score for disease severity recognition. A new approach in the treatment appears with the novel non biologic targeted synthetic disease-modifying antirheumatic drugs from the group of Janus kinase 1 and 3 (JAKI and JAK3), blocking interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15 and IL-21. We report a case of a 48-year-old patient who had suffered from polyarthritis from his age 40. Initial laboratory tests showed low inflammatory parameters and magnetic resonance imaging of both hands indicated an early stage of RA. Methylprednisolone and methotrexate therapy was initiated. The patient underwent additional tests, but there was not sufficient evidence for a precise diagnosis. According to the European League Against Rheumatism/American College of Rheumatology score-based algorithm, the patient was classified as seronegative RA based on joint involvement, duration of the disease, and synovitis not better explained by another disease. A partial clinical effect of the administered therapy (steroids as monotherapy and in combination, methotrexate and leflunomide) was noticed with the use of systemic steroids, but dramatic improvement was only achieved with a JAK inhibitor targeted therapy. Although the use of anti TNF-α blocker is a proposed procedure and the drug has not yet been registered in Europe, we took the opportunity to apply this new medication option. The patient, a construction worker, was treated for 20 months, which led to complete remission of the disease, without the need of basic or corticosteroid therapy. Full functional capacity necessary in his demanding job was also achieved. This result raised a question of timely introduction of immunomodulators in the polyarthritis treatment steps.


Identification of Zip8-correlated hub genes in pulmonary hypertension by informatic analysis.
Pulmonary hypertension (PH) is a syndrome characterized by marked remodeling of the pulmonary vasculature and increased pulmonary vascular resistance, ultimately leading to right heart failure and even death. The localization of Zrt/Irt-like Protein 8 (ZIP8, a metal ion transporter, encoded by SLC39A8) was abundantly in microvasculature endothelium and its pivotal role in the lung has been demonstrated. However, the role of Zip8 in PH remains unclear. Bioinformatics analysis was employed to identify SLC39A8 expression patterns and differentially expressed genes (DEGs) between PH patients and normal controls (NC), based on four datasets (GSE24988, GSE113439, GSE117261, and GSE15197) from the Biotechnology Gene Expression Omnibus (NCBI GEO) database. Gene set enrichment analysis (GSEA) was performed to analyze signaling pathways enriched for DEGs. Hub genes were identified by cytoHubba analysis in Cytoscape. Reverse transcriptase-polymerase chain reaction was used to validate SLC39A8 and its correlated metabolic DEGs expression in PH (SU5416/Hypoxia) mice. SLC39A8 expression was downregulated in PH patients, and this expression pattern was validated in PH (SU5416/Hypoxia) mouse lung tissue. SLC39A8-correlated genes were mainly enriched in the metabolic pathways. Within these SLC39A8-correlated genes, 202 SLC39A8-correlated metabolic genes were screened out, and seven genes were identified as SLC39A8-correlated metabolic hub genes. The expression patterns of hub genes were analyzed between PH patients and controls and further validated in PH mice. Finally, four genes (Fasn, Nsdhl, Acat2, and Acly) were downregulated in PH mice. However, there were no significant differences in the expression of the other three hub genes between PH mice and controls. Of the four genes, Fasn and Acly are key enzymes in fatty acids synthesis, Nsdhl is involved in cholesterol synthesis, and Acat2 is implicated in cholesterol metabolic transformation. Taken together, these results provide novel insight into the role of Zip8 in PH.


Loss of IP3R-BKCa Coupling Is Involved in Vascular Remodeling in Spontaneously Hypertensive Rats.
Mechanisms by which BKCa (large-conductance calcium-sensitive potassium) channels are involved in vascular remodeling in hypertension are not fully understood. Vascular smooth muscle cell (VSMC) proliferation and vascular morphology were compared between hypertensive and normotensive rats. BKCa channel activity, protein expression, and interaction with IP3R (inositol 1,4,5-trisphosphate receptor) were examined using patch clamp, Western blot analysis, and coimmunoprecipitation. On inside-out patches of VSMCs, the Ca2+-sensitivity and voltage-dependence of BKCa channels were similar between hypertensive and normotensive rats. In whole-cell patch clamp configuration, treatment of cells with the IP3R agonist, Adenophostin A (AdA), significantly increased BKCa channel currents in VSMCs of both strains of rats, suggesting IP3R-BKCa coupling; however, the AdA-induced increases in BKCa currents were attenuated in VSMCs of hypertensive rats, indicating possible IP3R-BKCa decoupling, causing BKCa dysfunction. Co-immunoprecipitation and Western blot analysis demonstrated that BKCa and IP3R proteins were associated together in VSMCs; however, the association of BKCa and IP3R proteins was dramatically reduced in VSMCs of hypertensive rats. Genetic disruption of IP3R-BKCa coupling using junctophilin-2 shRNA dramatically augmented Ang II-induced proliferation in VSMCs of normotensive rats. Subcutaneous infusion of NS1619, a BKCa opener, to reverse BKCa dysfunction caused by IP3R-BKCa decoupling significantly attenuated vascular hypertrophy in hypertensive rats. In summary, the data from this study demonstrate that loss of IP3R-BKCa coupling in VSMCs induces BKCa channel dysfunction, enhances VSMC proliferation, and thus, may contribute to vascular hypertrophy in hypertension.


Acute appendicitis in children: when does ultrasound help?
Fifty-six patients with possible appendicitis were evaluated clinically and by ultrasound. Ultrasound examination visualized the appendix in 18 of the patients evaluated and showed another pathology in six others. It was useful when the clinical picture was not clear (25 patients) as it showed an inflamed appendix in 10 patients. This was of particular value when there was another critical illness making clinical evaluation difficult (three patients), and for the diagnosis of other unsuspected pathological conditions (six patients). It did not affect the line of management when the clinical picture was clear enough to diagnose or exclude acute appendicitis.


Optic chiasm glioma, electrolyte abnormalities, nonobstructive hydrocephalus and ascites.
A 4-year-old girl with optic chiasm glioma (OCG), nonobstructive hydrocephalus and ventriculoperitoneal shunt is described, in whom marked ascites developed. The ascitic fluid was protein-rich and its amount correlated with cerebrospinal fluid (CSF) protein. The CSF protein level and the amount of ascitic fluid were influenced by chemotherapy. Very unusual hypernatremia, up to 190 mEq/l with no associated alteration in mental status, was also found. It is suggested that altered absorption ability owing to the high protein content was the cause of both the nonobstructive hydrocephalus and the ascites. The unusual well being with very high sodium concentrations may have resulted from osmoreceptor dysfunction, presumably caused by hypothalamic involvement as well as by the high CSF protein. This combination of findings may point toward specific characteristics of OCG. In an effort to reduce the amount of the ascitic fluid, a further chemotherapeutic trial may be done, before converting the shunt to the vetriculoatrial system.


Impact of Chronic Kidney Disease on the Presentation and Outcome of Patients Hospitalized With Atrial Fibrillation: Insights From Qatar.
Atrial fibrillation (AF) with coexistent chronic kidney disease (CKD) is poorly described in the literature. We compared the presenting symptoms, clinical characteristics, treatment, and outcome of patients hospitalized with AF with and without CKD in a large clinical registry. Data of patients hospitalized with AF between 1991 and 2012 in Qatar were analyzed. Of 5201 patients hospitalized for AF, 264 (5.1%) had CKD. Patients with AF and CKD were older with higher prevalence of other comorbidities and left ventricular dysfunction and were more likely to present with shortness of breath and chest pain compared with patients with AF alone who were more likely to present with palpitation. The crude in-hospital mortality was 3 times higher in patients with dual disease. On multivariable adjustments, CKD was an independent predictor of mortality (odds ratio: 2.84; 95% confidence interval: 1.33-6.08, P = .001). Further studies are warranted to try to reduce the increased mortality observed in this high-risk population.


Visible-laser desorption/ionization on gold nanostructures.
In this report, we describe the visible-laser desorption/ionization of biomolecules deposited on gold-coated porous silicon and gold nanorod arrays. The porous silicon made by electrochemical etching was coated with gold using argon ion sputtering. The gold nanorod arrays were fabricated by electrodepositing gold onto a porous alumina template, and the subsequent partial removal of the alumina template. A frequency-doubled/tripled Nd : YAG laser was used to irradiate the gold nanostructured substrate, and the desorbed molecular ions were mass-analyzed by a time-of-flight mass spectrometer. The desorption/ionization of biomolecules for both substrates was favored by the use of the 532-nm visible-laser, which is in the range of the localized surface plasmon resonance of the gold nanostructure. The present technique offers a potential analytical method for low-molecular-weight analytes that are rather difficult to handle in the conventional matrix-assisted laser desorption/ionization (MALDI) mass spectrometry.


Evaluation of dentin formed in autogenous tooth transplantation in the dog: a comparison between one- and two-stage surgical techniques.
This study was designed to compare the thickness of dentin formed associated with autogenous tooth transplantation in dogs, using either one- or two-stage surgical techniques. The study consisted of three Beagles, older than 5 months, in which six incisors and six premolars were transplanted to mechanically prepared recipient sockets. One group was transplanted using a one-stage method to recipient beds prepared immediately before transplantation. The second groups of teeth were transplanted using a two-stage method in which the recipient beds were prepared and left to heal for 7 days before transplantation. Dogs were injected with xylenol orange, calcein and oxytetracycline at 2 days before, 3 and 9 weeks after transplantation, respectively, for vital staining. Clinical examinations were carried out every week, and the animals were euthanized 9 weeks later. The jaws were resected, fixed in formaldehyde and embedded in resin. Undemineralized sections were cut and examined by fluorescent microscopy. The thickness of dentin formed in the third week after transplantation and 9 weeks was evaluated by undertaking histomorphometric analysis and analysed using the Mann-Whitney U test (P = 0.05). All the transplanted teeth in both groups survived, and the dentin was formed. No statistically significant difference was found in the thickness of dentin formed in the third week and formed in the third to ninth week between the treatment groups (P = 0.999 and P = 0.998, respectively). This study demonstrated that there was no difference between the two surgical techniques in terms of the thickness of dentin formed in transplanted teeth.


Green tea protects cytoskeleton from oxidative injury in cardiomyocytes.
Cardiac ischemia/reperfusion injury results in oxidative stress and poor physiological recovery. Episodes of hypoxia/reoxygenation (H/R) cause some subtle functional and structural alterations in sarcolemma, mithocondria, sarcoplasmic reticulum, nucleus, as well as cytoskeleton. In this report, by using cultured rat cardiomyocytes and laser confocal microscopy we have verified the possibility to counteract cytoskeleton alterations induced by H/R with the supplementation of an antioxidant agent, a green tea extract (GTE), and compared its effects to those of alpha-tocopherol. Moreover the effects of GTE on cell viability and cytosolic antioxidant activity have been evaluated. H/R induced myocardial damage occurs as histological alterations such as degeneration and disorganization of the cytoskeleton and loss of structural integrity of the nucleus. GTE supplementation increases cytosolic antioxidant activity and shows protective effects on cardiomyocyte cytoarchitecture and viability.


Luminescence Color and Intensity Changes of Nitridorhenium(V) Complexes Induced by Protonation/Deprotonation on the Bidentate Azolylpyridine Ligands.
Tricyanidonitridorhenium(V) complexes with azolylpyridines, namely, [ReN(CN)3(H-N2py)]- (1-H, H-N2py = 2-(3-pyrazolyl)pyridine) and [ReN(CN)3(L)]2- (2-a, L = 2-[1,2,3]-triazol-4-yl-pyridine anion (N3py-), and 3-a, that is, L = 2-(tetrazol-5-yl)-pyridine anion (N4py-)), were newly synthesized and characterized. The structures of the new complexes were determined by single-crystal X-ray analysis. The 1-H complex includes two geometrical isomers in which an isomer is the conformation with the pyridyl (py) and pyrazolyl (pyrz) moieties of H-N2py occupying the trans site to the nitrido (the ax site) and the trans site to the cyanido (the eq site), respectively, in a bidentate fashion; the other isomer is the py and pyrz moieties coordinated to the eq and ax sites. In 2-a and 3-a, the triazolyl (trz) and tetrazoly (tetrz) moieties in N3py- and N4py- occupy the eq site, and the py moieties in N3py- and N4py- coordinate to the ax site. The complex 1-H is deprotonated upon the addition of 1,8-diazabicyclo[5.4.0]undec-7-one or NaOH to produce [ReN(CN)3(N2py)]2- (1-a), and 2-a is protonated upon the addition of p-toluene sulfonic acid (TsOH) to give [ReN(CN)3(H-N3py)]- (2-H) in DMSO. The protonation reaction does not occur for 3-a with TsOH in DMSO. All the complexes show one-electron redox waves of the Re(VI)/Re(V) and azolylpyridine ligand-centered processes in 0.1 M (n-C4H9)4NPF6-DMSO. All the complexes exhibit photoluminescence in DMSO and in the crystalline phase at 296 K. The emissive excited states of the complexes in DMSO were assigned to MLCT with a spin triplet nature. The emission band shifts to shorter and longer wavelengths upon protonation and deprotonation of the coordinated azolylpyridines, respectively. The emission color and intensity changes of 2-H and 2-a in the presence of acidic and basic vapors were investigated.


Design of Interconnected Carbon Fiber Thermal Management Composites with Effective EMI Shielding Activity.
Heat dissipation efficiency and electromagnetic interference (EMI) shielding performance are vital to integration, miniaturization, and application of electronic devices. Flexible and designable polymer-based composites are promising candidates but suffer from unavoidable interfacial thermal resistances, anisotropic thermal conductivity, and low shielding of EMI limiting application. Herein, multifunctional epoxy resin (EP)-based composites with an interconnected carbon fibers (CFs) network structure containing a low thermal resistance interfacial were prepared by high-temperature calcination and infiltration. The coherent heat and electron transfer pathways constructed with self-oriented CFs cloth connected by carbon nanotubes (CNTs) converted from leaf-shaped zeolitic imidazolate frameworks (ZIF-L) and stable magnetic property provided by cobalt nanoparticles contained in the CNTs made composites to an integrated in-plane thermal conductivity of up to 7.50 W m-1 K-1, a through-plane thermal conductivity of 1.96 W m-1 K-1, and an EMI shielding effectiveness of 38.4 dB. Furthermore, the mechanical properties of CFs and the junction effect of CNTs endowed the composites with stability of mechanical property, thermal conductivity, and EMI shielding effectiveness after multiple bendings. The finite element simulation further verified the advantage of CFs network linked by CNTs on heat transfer. This work provides the desired design for the construction of a multifunctional polymer-based composite used in advanced electronic equipment.


The anti-oxidant effects are not the main mechanism for glutamine's protective effects on acute kidney injury in mice.
Acute kidney injury (AKI) is a common problem characterized by an inflammatory response in the kidney and oxidative stress. However, there are no interventions to prevent AKI. Glutamine is an important precursor of glutathione and has also been shown to induce heat shock proteins (HSP). Thus, glutamine may affect both oxidative stress and inflammation. This study was to explore the effects of glutamine pretreatment on nephrotoxic AKI and to investigate the underlying mechanisms. First, the effects of alternate doses of glutamine were compared in CD-1 mice with AKI induced with folic acid intra-peritoneal injection. Then the effects of glutamine quercetin (an HSP inhibitor), and quercetin+glutamine, were compared in the same AKI model. AKI were assessed with plasma creatinine, urine neutrophil gelatinase-associated lipocalin, and renal histology. Inflammatory response was monitored with renal tumor necrosis factor (TNF-α), chemkines (CXCL1 and CCL2) contents, and neutrophil infiltration. Oxidative injury was detected with reduced glutathione, malondialdehyde, and protein thiol. Glutamine provided dose-dependent renal protection. Pretreatment with quercetin, which was showed to inhibit HSP-70 expression, abolished glutamine's renal-protective effects. Quercetin also abrogated glutamine's beneficial effects on renal TNF-α, chemokines, and neutrophil infiltration. However, quercetin did not affect glutamine's anti-oxidative effects. These results suggest that glutamine's renal-protective effects are mainly related to its activation of HSP-70, which mitigates inflammatory response, renal neutrophil infiltration and subsequent AKI. Regulating neutrophil infiltration might be a potential therapeutic target for AKI.


Calcium antagonistic vasodilator mechanisms of brovincamine fumarate studied in canine cerebral artery.
In order to elucidate the major mechanism of cerebral vasodilator action of brovincamine fumarate (CAS 57475-17-9) the present study was performed comparing its effects with those of d-cis-diltiazem in the isolated canine basilar artery. Brovincamine possessed a wide spectrum of inhibitory actions on the contractions of the artery produced by various spasmogens and mechanical stretch. Brovincamine was 3 to 40 times less potent than d-cis-diltiazem in the inhibitory actions. Simultaneous recordings of intracellular Ca2+ concentration and mechanical activity showed that brovincamine and d-cis-diltiazem decreased both parameters augmented by high KCl in a concentration-dependent and parallel manner. Both brovincamine and d-cis-diltiazem shifted parallel to the right the concentration-response curves for CaCl2-induced contraction of the artery constructed in the Ca(2+)-free depolarizing medium. Furthermore, Schild regression of the curves was linear with a slope of unity, indicating apparently a competitive antagonism between Ca2+ channel function/Ca2+ and brovincamine or d-cis-diltiazem. The results suggest that the cerebral vasodilator effect of brovincamine is mainly attributable to the inhibition of Ca2+ influx through the voltage-dependent Ca2+ channels, supporting the reported clinical benefits of this drug in the treatment of cerebrovascular disorders.


Making It to Sustainability: Evaluating Billing Strategies for Collaborative Care.
The collaborative care model (CoCM) is an effective strategy to manage common mental disorders in primary care. Despite the growing adoption of newer CoCM billing codes to support these programs, few studies have investigated the use of these codes. This column evaluated the implementation of CoCM billing codes by comparing clinics using different billing strategies and assessed the impact of CoCM code implementation on revenue and on clinical and process-of-care outcomes. Qualitative data were obtained to understand provider perspectives. The results indicate that CoCM billing code implementation is operationally feasible, does not adversely affect the delivery of patient care or revenue, and is acceptable to providers.


Evidence that ingested nitrate and nitrite are beneficial to health.
The literature was reviewed to determine whether ingested nitrate or nitrite may be detrimental or beneficial to human health. Nitrate is ingested when vegetables are consumed. Nitrite, nitrate's metabolite, has a long history of use as a food additive, particularly in cured meat products. Nitrite has been a valuable antibotulinal agent in cured meats and may offer some protection from other pathogens in these products as well. Nitrite's use in food has been clouded by suspicions that nitrite could react with amines in the gastric acid and form carcinogenic nitrosamines, leading to various cancers. Nitrate's safety has also been questioned, particularly with regard to several cancers. Recently, and for related reasons, nitrite became a suspected developmental toxicant. A substantial body of epidemiological evidence and evidence from chronic feeding studies conducted by the National Toxicology Program refute the suspicions of detrimental effects. Recent studies demonstrate that nitrite, upon its ingestion and mixture with gastric acid, is a potent bacteriostatic and/or bactericidal agent and that ingested nitrate is responsible for much of the ingested nitrite. Acidified nitrite has been shown to be bactericidal for gastrointestinal, oral, and skin pathogenic bacteria. Although these are in vitro studies, the possibility is raised that nitrite, in synergy with acid in the stomach, mouth, or skin, may be an element of innate immunity.


A novel Caldicott-compliant hospital imaging protocol for open fracture photography.
Open fractures incur significant morbidity and mortality, and as such have standardised guidelines for their management. Photography of open fractures is an essential component of documentation in the treatment of open fractures as per the British Orthopaedic Association Standards of Trauma and National Institute for Health and Care Excellence guidelines. Smartphones have made photography easily accessible to the clinician, but serious concerns exist regarding data security and the consent process around the use of sensitive clinical images. This project sought to overcome this issue by developing a Caldicott-compliant hospital imaging protocol that allows clinicians to use their smartphone to upload open fracture images into the patient's permanent record. Implementation of the protocol was audited and resulted in the increase of safe and secure open fracture photographic storage to inpatient medical records. This protocol would be transferrable to other hospital trusts and could be adopted across major trauma networks.


Elucidation, quantitative refinement, and in vivo utilization of the HOXA13 DNA binding site.
Mutations in Hoxa13 cause malformations of the appendicular skeleton and genitourinary tract, including digit loss, syndactyly, and hypospadias. To determine the molecular basis for these defects, the DNA sequences bound by HOXA13 were empirically determined, revealing a novel high affinity binding site. Correlating the utilization of this high affinity binding site with genes exhibiting perturbed expression in Hoxa13 mutant limbs, we identified that HOXA13 suppresses the expression of the BMP antagonist, Sostdc1. In the absence of HOXA13 function, Sostdc1 is ectopically expressed in the distal limb, causing reduced expression of BMP-activated genes and decreased SMAD phosphorylation. Limb chromatin immunoprecipitation revealed HOXA13 binding at its high affinity site in two conserved Sostdc1 regulatory sites in vivo. In vitro, HOXA13 represses gene expression through the Sostdc1 high affinity binding sites in a dosage-dependent manner. Together, these findings confirm that the high affinity HOXA13 binding site deduced by quantitative analyses is used in vivo to facilitate HOXA13 target gene regulation, providing a critical advance toward understanding the molecular basis for defects associated with the loss of HOXA13 function.


Course and outcome in panic disorder: a review of recent follow-up studies.
This paper reviews the methodologic considerations that are important in evaluating and interpreting panic disorder outcome studies and the results of the most well-designed of these studies. Sixteen studies that used modern diagnostic criteria and interviewed at least 25 patients on at least two occasions over a minimum follow-up period of one year are reviewed. Results show that, despite the availability of effective anti-panic treatments, panic disorder remains a chronic illness. While most patients improve, few are "cured." The presence of agoraphobia, major depression and personality disorder seems to predict poorer outcome. The importance of measuring multiple clinical dimensions of panic is emphasized, along with the need to reach a consensus about the definition of "outcome" and the particular instruments to use to measure it.


Analysis of microsatellite DNA using a non-radioactive method: blotting from polyacrylamide gel to nylon membrane using a gel dryer with subsequent hybridization to digoxigenin-labelled (dCdA)8 oligonucleotide probes.
A non-radioactive method for the analysis of microsatellite DNA polymorphisms (mainly (CA)n-repeats) is described. Variation in length of (CA)n and (GT)n blocks was demonstrated directly by amplification of DNA from within and immediately flanking the repeat blocks using the polymerase chain reaction. The amplified DNA was resolved on a denaturing polyacrylamide gel, transferred to a nylon membrane using a gel dryer, and subsequently hybridized with digoxigenin-labelled (dCdA)8 oligonucleotide probes. This method enables easy and rapid analysis of polymorphic microsatellite DNA.