[Cellular immune responses of recombinant hepatitis B (rHB) vaccine and HBsAG derived from Hansenula polymorpha cells].
To study the kinetics of immune response in mice and human immunized with rHB vaccine or rHBsAg derived from yeast cells (Hansenula polymorpha). With different doses,the level of IFN-gamma secreted by spleen mononuclear cells (MNC) including CD8+ T cells by MACs of mice were detected by enzyme-linked immunospot (ELISPOT) methods after stimulation in vitro with HBsAg MHC class I peptide S28-39, respectively. At serial time points, the immunized mice were detected for IFN-gamma by ELISPOT as above and for the lymphocytotoxicity test (CTL) by specific lysis assay. The levels of IFN-gamma, IL-2, IL-5 and anti-HBs in mice induced by rHB vaccine were detected after single or three doses. Four adults were vaccinated with rHB vaccine according to 0, 1 and 2 month schedule. The peripheral blood mononuclear cells (PBMCs) were collected at the 3, 8, 21, 34 and 65 days after the first dose. The CD8+ T cells with high purity obtained by sorting from PBMCs were stimulated with rHBsAg or HBsAg peptides. The SFC of IFN-gamma, IL-2 and IL-4 of CD4+ and CD8+ T cells were determined by ELISPOT. The cytokine of IFN-gamma became detectable on day 7 and its peak value appeared on day 14 by ELISPOT. The CTL was detected on day 7 and the maximum lysis of CTL appeared on day 28. The cellular immune response of IFN-gamma of MNCs were significantly correlated with the doses vaccinated from 1 microg to 8 microg (r(positive rates) = 0.951, P(positive rates) = 0.049 < 0.05; r(SFC) = 0.996, P(SFC) = 0.000 < 0.05). IFN-gamma SFC of CD+ T cells were significantly associated with the doses from 1 microg to 4 microg (r = 0.999, P = 0.025 < 0.05). The HBsAg specific cellular immune an d humoral responses of mice immunized with three doses were significantly higher than that with a single dose (P < 0.05). The characteristics of IFN-gamma, IL-2 and IL-4 of CD4+ and CD8+ T cells were variable between individuals immunized with the same rHB vaccine. The level of IL-2 and IL-4 of responders were significantly related to the titer of anti-HBs. Data from this study showed the kinesis of cellular immunity in mice and adults vaccinated with rHBsAg or rHB vaccine respectively, and the characteristics of cellular immune response in adults induced by the vaccine. Our data provided the basis of standardizing the analysis of cellular immune response to rHB vaccine.


Interferon activation of "pre-spontaneous killer" (pre-SK) cells and alteration in kinetics of lysis of both "pre-SK" and active SK cells.
Interferon augments spontaneous killer cellular cytotoxicity (SKCC). This modulation may be vital in both tumor resistance and host viral defenses. To date, whether increased numbers of effector cells or activation of individual effector cells is responsible for this augmentation has not been established. Using a single cell assay where SK killing is directly visualized by the reading of trypan blue uptake at various time points by effector-target cell conjugates plated in agarose gel, we measured in vitro alterations in percentage of conjugate formation, number of active SK cells, and kinetics of SK cell lysis at the single cell level after 1 hr of interferon incubation. After interferon, there is no difference in number of cells that bind K-562 targets. This augmentation of cytotoxicity is due to both recruitment of new effector cells and an activation of the lytic process of both the new and already active SK cells.


The radiology informed consent form: recommendations from the European Society of Cardiology position paper.
Every radiological and nuclear medicine examination confers a definite long-term risk of cancer, but most patients undergoing such examinations receive no or inaccurate information about radiation dose and corresponding risk related to the dose received. Informed consent is a procedure to support (not substitute) the physician/patient dialogue and relationship, facilitating a free, informed and aware expression of the patient's will in the principle of patient autonomy. Physicians are responsible for providing patients with all the information on risks, benefits and alternatives useful to the patient to make the decision. In current radiological practice the information on the radiation dose and long-term cancer risks is difficult to find and not easy to understand. The form using plain language should spell-out the type of examination, the effective dose (mSv), the effective dose expressed in number of chest radiographs and the risk of cancer. The current practice clashes against the guidelines and the law.


The Chaoborus pump: Migrating phantom midge larvae sustain hypolimnetic oxygen deficiency and nutrient internal loading in lakes.
Hypolimnetic oxygen demand in lakes is often assumed to be driven mainly by sediment microbial processes, while the role of Chaoborus larvae, which are prevalent in eutrophic lakes with hypoxic to anoxic bottoms, has been overlooked. We experimentally measured the respiration rates of C. flavicans at different temperatures yielding a Q10 of 1.44-1.71 and a respiratory quotient of 0.84-0.98. Applying the experimental data in a system analytical approach, we showed that migrating Chaoborus larvae can significantly add to the water column and sediment oxygen demand, and contribute to the observed linear relationship between water column respiration and depth. The estimated phosphorus excretion by Chaoborus in sediment is comparable in magnitude to the required phosphorus loading for eutrophication. Migrating Chaoborus larvae thereby essentially trap nutrients between the water column and the sediment, and this continuous internal loading of nutrients would delay lake remediation even when external inputs are stopped.


Critical Assessment of Condensate Boundaries in Dual-Color Single Particle Tracking.
Biomolecular condensates are membraneless cellular compartments generated by phase separation that regulate a broad variety of cellular functions by enriching some biomolecules while excluding others. Live-cell single particle tracking of individual fluorophore-labeled condensate components has provided insights into a condensate's mesoscopic organization and biological functions, such as revealing the recruitment, translation, and decay of RNAs within ribonucleoprotein (RNP) granules. Specifically, during dual-color tracking, one imaging channel provides a time series of individual biomolecule locations, while the other channel monitors the location of the condensate relative to these molecules. Therefore, an accurate assessment of a condensate's boundary is critical for combined live-cell single particle-condensate tracking. Despite its importance, a quantitative benchmarking and objective comparison of the various available boundary detection methods is missing due to the lack of an absolute ground truth for condensate images. Here, we use synthetic data of defined ground truth to generate noise-overlaid images of condensates with realistic phase separation parameters to benchmark the most commonly used methods for condensate boundary detection, including an emerging machine-learning method. We find that it is critical to carefully choose an optimal boundary detection method for a given dataset to obtain accurate measurements of single particle-condensate interactions. The criteria proposed in this study to guide the selection of an optimal boundary detection method can be broadly applied to imaging-based studies of condensates.


Effects of selective adrenergic agonists and antagonists on gastric tone in the rat.
The aim of the present in vivo study was to investigate in anaesthetized rats, the effects of selective adrenergic agonists and antagonists on basal gastric tone and phasic contractions by the use of a volumetric method. L-phenylephrine, an alpha-1 agonist, induced hypertension, bradycardia and a significant gastric relaxation. Clonidine, an alpha-2 agonist, caused hypotension, bradycardia and a significant gastric contraction and a reduction of the amplitude of phasic contractions. Salbutamol, a beta-2 agonist, induced a dose-dependent tachycardia and a significant inhibition of gastric tone whereas prenalterol, a beta-1 agonist, induced tachycardia without any significant influence on gastric basal tone. Yohimbine, an alpha-2 blocker, significantly decreased gastric basal tone and reversed the inhibition of phasic contractions induced by clonidine. Prazocine, a selective alpha-1 blocker, and propranolol, a non-selective beta-blocker, had no significant influence on gastric basal tone or phasic contractions. It is concluded that sympathetic inhibition of basal gastric tone in the rat is mediated by alpha-1 and beta-2 adrenergic receptors. Activation of alpha-2 adrenergic receptors significantly increased basal gastric tone and reduced the amplitude of phasic contractions. A blockade of alpha-2 receptors significantly decreased basal gastric tone and restored the amplitude of phasic contractions.


Effect of patterned polyacrylamide hydrogel on morphology and orientation of cultured NRVMs.
We recently demonstrated that patterned Parylene C films could be effectively used as a mask for directly copolymerizing proteins on polyacrylamide hydrogel (PAm). In this work, we have proved the applicability of this technique for studying the effect such platforms render on neonatal rat ventricular myocytes (NRVMs). Firstly, we have characterised topographically and mechanically the scaffolds in liquid at the nano-scale level. We thus establish that such platforms have physical properties that closely mimics the in vivo extracellular environment of cells. We have then studied the cell morphology and physiology by comparing cultures on flat uniformly-covered and collagen-patterned scaffolds. We show that micro-patterns promote the elongation of cells along the principal axis of the ridges coated with collagen. In several cases, cells also tend to create bridges across the grooves. We have finally studied cell contraction, monitoring Ca2+ cycling at a certain stimulation. Cells seeded on patterned scaffolds present significant responses in comparison to the isotropic ones.


Congenital kaposiform hemangioendothelioma with Kasabach-Merritt phenomenon successfully treated with low-dose radiation therapy.
Kaposiform hemangioendothelioma (KHE) associated with Kasabach-Merritt phenomenon is a life-threatening vasculopathy. The current mainstay treatment for KHEs is corticosteroids and chemotherapy, but these medications do not work for all patients and carry significant side effects. We report a neonate with a large congenital KHE who responded extremely well to low-dose radiation therapy.


Wearable Potentiometric Sensors for Medical Applications.
Wearable potentiometric sensors have received considerable attention owing to their great potential in a wide range of physiological and clinical applications, particularly involving ion detection in sweat. Despite the significant progress in the manner that potentiometric sensors are integrated in wearable devices, in terms of materials and fabrication approaches, there is yet plenty of room for improvement in the strategy adopted for the sample collection. Essentially, this involves a fluidic sampling cell for continuous sweat analysis during sport performance or sweat accumulation via iontophoresis induction for one-spot measurements in medical settings. Even though the majority of the reported papers from the last five years describe on-body tests of wearable potentiometric sensors while the individual is practicing a physical activity, the medical utilization of these devices has been demonstrated on very few occasions and only in the context of cystic fibrosis diagnosis. In this sense, it may be important to explore the implementation of wearable potentiometric sensors into the analysis of other biofluids, such as saliva, tears and urine, as herein discussed. While the fabrication and uses of wearable potentiometric sensors vary widely, there are many common issues related to the analytical characterization of such devices that must be consciously addressed, especially in terms of sensor calibration and the validation of on-body measurements. After the assessment of key wearable potentiometric sensors reported over the last five years, with particular attention paid to those for medical applications, the present review offers tentative guidance regarding the characterization of analytical performance as well as analytical and clinical validations, thereby aiming at generating debate in the scientific community to allow for the establishment of well-conceived protocols.


Prevention of atopic disorders.
Prevention of sensitization, onset of disease and disease exacerbations is a very important aspect of holistic approach towards allergic disorders. The prevalence of allergic or atopic disorders has increased significantly in children over the last three decades. There are significant variations in prevalence between countries and also within many countries. Environmental factors obviously play a major role. Environmental allergens are responsible for sensitisation, disease and exacerbations of disease symptoms. Preventive strategies at each level are important: Primary prevention is to stop the process of sensitisation and secondary prevention to prevent re-exposures or prolonged exposure in those who have become sensitized while tertiary prevention is to reduce or minimise morbidity. Various allergen avoidance measures are discussed, with reference to India so that physicians can incorporate these in the management not only of atopic patients but also as preventive strategy in high risk families.


Macrophage-mediated suppression of con A-induced IL-2 production in spleen cells from syphilitic rabbits.
Blast transformation studies have indicated a diminished T cell response in spleen cell preparations from rabbits infected with Treponema pallidum. IL-2 synthesis by T lymphocytes is required for proliferation of these cells. Thus, Con A-induced IL-2 generation was measured in syphilitic animals infected for 9 to 14 days. IL-2 production in the infected rabbits was only one-half that observed for uninfected rabbits. This marked decrease in IL-2 was not caused by decreased IL-1 secretion by adherent cells from infected animals because similar levels were found in both infected and uninfected splenic cultures. This decrease was also not caused by an increase in infected spleen cell adsorption of IL-2; similar numbers of receptors for this IL were present in Con A-stimulated infected and uninfected splenic preparations. The inhibited IL-2 production in infected spleen cells was reversed upon removal of the adherent cells and also elevated upon addition of indomethacin to the cultures. PGE levels were also elevated in splenic cultures from infected animals. Finally, IL-2 synthesis, when evaluated at various days postinfection, showed that at 4 days, splenic cells generated twice as much IL-2 as uninfected cells. At 9 to 14 days, IL-2 levels were dramatically decreased (50% lower than that observed in uninfected cultures), and suppression of IL-2 by adherent cells was observed as late as 35 days post-infection. We propose that premature down regulation (suppression) of IL-2 secretion is mediated by adherent cells via a cyclo-oxygenase product, most likely PGE. These results may explain why most, but not all, treponemes are cleared during infection, and why the secondary manifestations of the disease occur.


Respiratory syncytial virus and influenza. Practical community surveillance.
Concurrent and sequential outbreaks of infection with respiratory syncytial virus (RSV) and influenza A virus were studied, utilizing a local surveillance system for infectious diseases that involved weekly reports from primary care physicians. The patterns of illness in the community and in hospital admissions were relatively specific for these two viruses, and differed according to whether RSV and influenza A virus occurred together or separately. This surveillance system appeared to be a practical and accurate indicator of the activity of RSV and influenza A virus in the community. Such a system may serve as a valuable means of relatively early detection of the local arrival of these viruses, and recognition of these illness patterns might aid the physician in diagnosis.


Electron microscopic study of the open circulatory system of the shrimp, Caridina japonica. I. Gill capillaries.
The ultrastructure of the phyllobranchiate type gill of the shrimp, Caridina japonica, was studied. The most characteristic feature of the open circulatory system of Cardina is the vascular lumen of the gill capillaries which is considered to be the interstitial space. The following observations substantiate this view: (1) a thin fibrous layer forms the innermost structure of the walls of gill capillaries and is in direct contact with the blood stream; (2) filaments in the fibrous layer are assumed to correspond to the reticular fibers in the interstitial space of the alveolar wall of mammals; (3) the absence of the endothelium as well as the endothelial basal lamina which are the essential structural components of the closed circulatory system in vertebrates. The gill epithelium contains intermediate, septate and tight junctions. The first two form a junctional complex near the apical cell border and may function as a permeability barrier by occluding the intercellular space as well as functioning in electrical coupling and cellular adhesion. The tight junction is spot-like and may serve no role in the function of the permeability barrier.


The PRIDE proteomics identifications database: data submission, query, and dataset comparison.
The PRIDE database has been developed to allow the proteomics community to share publicly, or within private collaborations, the vast volume of data generated by proteomics laboratories across the globe. These data are being generated at an expanding rate as increasingly sophisticated technologies become available. Compounding this problem, the infrastructure and techniques used to generate these data vary in terms of the instrumentation used, the protein sequence databases searched, the search engines employed, and the automatic or manual filtering of identifications following the initial automated search. The PRIDE project provides an infrastructure to solve these problems, including a generic, standards-based format that can be annotated to capture data generated using any proteomics pipeline, a protein accession mapping service to overcome the problem of disparate protein sequence databases being searched, and tools for query, comparison, and analysis of proteomics data. This chapter describes the main practical considerations in making use of PRIDE, including the available resources: the PRIDE database, the Ontology Lookup Service (OLS), the protein identifier cross-referencing service (PICR), the Proteome Harvest PRIDE submission spreadsheet, and the PRIDE BioMart.PRIDE can be accessed at http://www.ebi.ac.uk/pride.


Differential expression and functionality of TRPA1 protein genetic variants in conditions of thermal stimulation.
The role of genetic modifications of the TRPA1 receptor has been well documented in inflammatory and neuropathic pain. We recently reported that the E179K variant of TRPA1 appears to be crucial for the generation of paradoxical heat sensation in pain patients. Here, we describe the consequences of the single amino acid exchange at position 179 in the ankyrin repeat 4 of human TRPA1. TRPA1 wild type Lys-179 protein expressed in HEK cells exhibited intact biochemical properties, inclusive trafficking into the plasma membrane, formation of large protein complexes, and the ability to be activated by cold. Additionally, a strong increase of Lys-179 protein expression was observed in cold (4 °C) and heat (49 °C)-treated cells. In contrast, HEK cells expressing the variant Lys-179 TRPA1 failed to get activated by cold possibly due to the loss of ability to interact with other proteins or other TRPA1 monomers during oligomerization. In conclusion, the detailed understanding of TRPA1 genetic variants might provide a fruitful strategy for future development of pain treatments.


Insulin-producing β-cells regenerate ectopically from a mesodermal origin under the perturbation of hemato-endothelial specification.
To investigate the role of the vasculature in pancreatic β-cell regeneration, we crossed a zebrafish β-cell ablation model into the avascular npas4l mutant (i.e. cloche). Surprisingly, β-cell regeneration increased markedly in npas4l mutants owing to the ectopic differentiation of β-cells in the mesenchyme, a phenotype not previously reported in any models. The ectopic β-cells expressed endocrine markers of pancreatic β-cells, and also responded to glucose with increased calcium influx. Through lineage tracing, we determined that the vast majority of these ectopic β-cells has a mesodermal origin. Notably, ectopic β-cells were found in npas4l mutants as well as following knockdown of the endothelial/myeloid determinant Etsrp. Together, these data indicate that under the perturbation of endothelial/myeloid specification, mesodermal cells possess a remarkable plasticity enabling them to form β-cells, which are normally endodermal in origin. Understanding the restriction of this differentiation plasticity will help exploit an alternative source for β-cell regeneration.


Unraveling the Mechanism of Very Initial Dendritic Growth Under Lithium Ion Transport Control in Lithium Metal Anodes.
Lithium metal deposition is strongly affected by the intrinsic properties of the solid-electrolyte interphase (SEI) and working electrolyte, but a relevant understanding is far from complete. Here, by employing multiple electrochemical techniques and the design of SEI and electrolyte, we elucidate the electrochemistry of Li deposition under mass transport control. It is discovered that SEIs with a lower Li ion transference number and/or conductivity induce a distinctive current transition even under moderate potentiostatic polarization, which is associated with the control regime transition of Li ion transport from the SEI to the electrolyte. Furthermore, our findings help reveal the creation of a space-charge layer at the electrode/SEI interface due to the involvement of the diffusion process of Li ions through the SEI, which promotes the formation of dendrite embryos that develop and eventually trigger SEI breakage and the control regime transition of Li ion transport. Our insight into the very initial dendritic growth mechanism offers a bridge toward design and control for superior SEIs.


Why treatment efficacy on breathlessness in laboratory but not daily life trials? The importance of standardized exertion.
Treatments for chronic breathlessness, including opioids and oxygen, have shown efficacy in the controlled laboratory setting, whereas effects have been inconsistent or absent in trials in daily life. This review discusses the lack of standardized exertion as a potential cause of false negative findings for breathlessness in daily life. The level of breathlessness can be modified by patients by changing their level of physical activity. Effects of opioids and oxygen have been shown at standardized level of exertion (iso-time) but not at the end of symptom-limited (peak) exertion. Trials in daily life reporting no effects on breathlessness did not standardize the exertion or employed insensitive methods, such as the 6-min walk test that should not be used for measuring breathlessness. Novel tests - the 3-min walk and stepping tests have been validated in chronic obstructive pulmonary disease and are responsive for measuring change in breathlessness. Breathlessness should be measured at standardized exertion, otherwise treatment effects may be biased or overlooked. Tests for valid measurement of breathlessness in clinical practice and daily life are available and emerging.


Sesamin exerts anti-tumor activity in esophageal squamous cell carcinoma via inhibition of TRIM44 and NF-κB signaling.
Tripartite motif-containing 44 (TRIM44) is known to play an oncogenic role in multiple human cancers, including esophageal cancer. Sesamin possesses potent anti-inflammatory and anti-cancer properties for various cancers. This study is designed to unravel the biological functions of sesamin and TRIM44 in esophageal cancer. TRIM44 expression in esophageal squamous cell cancer (ESCC) cell lines and tissues was determined by RT-qPCR assay and Western blot. The effects of sesamin and TRIM44 on ESCC cell growth in vivo and in vitro were assessed by the mouse model and CCK-8 assay, respectively. We found that TRIM44 was significantly upregulated in ESCC cell lines and tissues when compared to their counterparts. Sesamin treatment or depletion of TRIM44 markedly reduced ESCC cell proliferation. The nuclear factor kappa B (NF-κB) and toll-like receptor 4 (TLR4) signaling pathway may be involved in sesamin-mediated TRIM44 suppression. Finally, we showed that oral administration of sesamin dramatically inhibited tumor growth or ESCC in nude mice. Our results suggest that sesamin exerts anti-tumor activity in ESCC via inhibition of NF-κB signaling pathway, demonstrating its potential for the treatment of esophageal cancer.


Tetrapod-type [Asp1] angiotensin is present in a holostean fish, Amia calva.
The renin-angiotensin system has been identified in various vertebrates, from elasmobranchs to mammals. Tetrapod (amphibians to mammals) angiotensin (ANG) has Asp at the N-terminus, but Asp is replaced by Asn in elasmobranch and teleost fish. ANG I has been isolated from incubates of plasma and kidney extracts of the bowfin Amia calva, a holostean fish, using the eel vasopressor activity as an assay system; its sequence was found to be H-Asp-Arg-Val-Tyr-Val-His-Pro-Phe-Asn-Leu-OH after sequence analysis, mass spectrometry, and comparison with the synthetic peptide. This sequence is identical to bullfrog ANG I. [Asn1] ANG I was not detected. Thus the bowfin is the first fish species which contains only [Asp1] ANG I. The bowfin ANG I and II were no more vasopressor than eel peptides in the bowfin, indicating that bowfin ANG II receptors do not distinguish between [Asp1] and [Asn1] peptides. In the rat, bowfin ANG I and rat [Ile5, His9] ANG I have equipressor activities when examined in different animals, but the vasopressor activity of bowfin ANG I decreased following rat ANG I in the same animals, although the activity of rat ANG I was unaffected after bowfin ANG I. The present study directly demonstrates the presence of the renin-angiotensin system in a holostean fish and showed that its ANG II receptors have not yet fully coevolved with the homologous [Asp1] peptide.


Biphasic response to dobutamine predicts improvement of global left ventricular function after surgical revascularization in patients with stable coronary artery disease: implications of time course of recovery on diagnostic accuracy.
This study sought to evaluate the time course of improvement of left ventricular (LV) dysfunction in stable patients and its implications on the accuracy of dobutamine echocardiography for predicting improvement after surgical revascularization. Little is known about the optimal timing for evaluation of postrevascularization recovery of the contractile function of viable myocardium. Sixty-one patients with chronic ischemic LV dysfunction scheduled for elective surgical revascularization were prospectively selected. They underwent dobutamine echocardiography (5 to 40 microg/kg body weight per min) and radionuclide ventriculography both preoperatively and at 3-month follow-up. At 14 months, another evaluation of LV function was obtained. To analyze echocardiograms, a 16-segment model and a five-point scoring system were used. Dyssynergic segments were considered likely to recover in the presence of a biphasic contractile response to dobutamine. Improvement of global function was defined as a > or =5% increase in LV ejection fraction (LVEF). Of the 61 patients, LVEF improved in 12 at 3 months and in 19 at late follow-up (from 32+/-8% to 42+/-9%, p < 0.0001). The frequency and time course of improvement of LVEF were similar in patients with mild and severe LV dysfunction. A biphasic response, identified in 186 of the 537 dyssynergic segments, was predictive of recovery in 63% at 3 months and in 75% at late follow-up. The positive predictive value was best in the most severe dyssynergic segments (90% vs. 67%). Other responses were highly predictive for nonrecovery (92%). The sensitivity and specificity for improvement of global function on a patient basis (> or =4 biphasic segments) were 89% and 81%, respectively, at late follow-up. Serial postoperative follow-up studies demonstrate incomplete recovery of contractile function at 3 months. The diagnostic accuracy of dobutamine echocardiography for predicting recovery is dependent on three factors: the combining of low and high dobutamine dosages, the severity of regional dyssynergy and the timing of evaluation.


[The ultrastructural changes occurring in the endometrium of women who use intrauterine pessaries].
The authors studied ultrastructural changes in the endometrium of 25 women, using intrauterine contraceptive devices, preventing conception, during various time limits. The material of the endometrial biopsy was fixed with glutar and osmium in a phosphate buffer and embedded in durcopan. Section were prepared by a microtome and observed under electron microscope of Hitachi type. Comparing the parameters duration of usage of loops and character of changes in the endometrium an impression was obtained that the usage of contraceptive intrauterine devices for one-year period did not induced changes of pathological character. Functional changes in the endometrium occurred after a two-year stay of the loop in the uterus as there were inflammatory changes of spot-like character in two of the sections. Local areas of inflammation of nonspecific character, manifested under the form of lymphocytes and leucocyte accumulation, were found in women with long usage of contraceptive intrauterine devices. The authors advise to remove the loop 2.5-3 years after its application and to wait for the complete regeneration of the endometrium.


Bioactivation of 6-aminochrysene by animal and human hepatic preparations: contributions of microsomal and cytosolic enzyme systems.
6-Aminochrysene was converted into mutagen(s), in the Ames test in the presence of Aroclor 1254-induced hepatic S9, microsomal and cytosolic fractions, the first being the least and the last the most efficient activation system. The cytosolic activation of 6-aminochrysene decreased in the presence of increasing amounts of microsomes. The Aroclor 1254-induced rat microsomal and cytosolic systems differed markedly in a number of properties, including their cofactor requirements and responses to prototype inducers of the cytochrome P450-dependent mixed-function oxidase system. The cytosolic activation system could also convert 2-aminochrysene to mutagens but not 2- and 6-methylchrysene. Human hepatic cytosol could convert 6-aminochrysene and 2-aminoanthracene to mutagens in the Ames test. It is concluded that a hepatic cytosolic oxygenase exists, totally different from the microsomal oxygenases, which metabolizes aminopolycyclic aromatic hydrocarbons to mutagens, presumably through N-oxidation. This oxygenase activity appears to be present in human hepatic cytosol.


Temporal bone histopathology over 15 years post-stapedectomy.
Twenty-three temporal bones from 14 patients who had undergone stapedectomy more than 15 years (the longest, 28 years) preceding death were studied microscopically. Although a foreign body reaction was still found in the ears with a polyethylene prosthesis, it was seldom found in the ears with a wire or Teflon prosthesis. As the resorption of the incus was not severe, it was suggested that it occurred in the early stage of post-stapedectomy and the structural condition of the incus and prosthesis was stable for a long time (even over 15 years) after stapedectomy. In all ears, the grafts on the oval window continued to be the adequate barrier between the middle ear and inner ear. Even though cupping of the graft membrane was frequently found, it seemed not to disturb the sound conduction. The depth of the cupping was correlated somewhat with the thickness of the graft.


IL-17A enhances vitamin D3-induced expression of cathelicidin antimicrobial peptide in human keratinocytes.
Cathelicidin is strongly expressed in lesional skin in psoriasis and may play an important role as both an antimicrobial peptide and as an autoinflammatory mediator in this chronic skin disease. The mechanism of increased cathelicidin in psoriatic keratinocytes is not known, but recent observations have found that psoriasis has abundant Th17 cells that produce IL-17A and IL-22. We found that human keratinocytes stimulated with supernatants from T cells isolated from lesional psoriatic skin increased expression of cathelicidin when stimulated in the presence of 1,25-dihydroxyvitamin D(3) (1,25D(3)). This increase was signaled through the IL-17RA. In vitro, IL-17A, but not IL-22, enhanced cathelicidin mRNA and peptide expression in keratinocytes dependent on the presence of 1,25D(3). At the same time, coincubation with 1,25D(3) blocked induction of human beta-defensin 2 (HBD2), IL-6, and IL-8, which are other target genes of IL-17A. Act1, an adaptor associated with IL-17RA and essential for IL-17A signaling, mediated cathelicidin induction, as its suppression by small interfering RNA inhibited HBD2 and cathelicidin. Both, 1,25D(3) and IL-17A signaled cathelicidin induction through MEK-ERK. These results suggest that increased IL-17A in psoriatic skin increases cathelicidin through a vitamin D(3)-, Act1-, and MEK-ERK-dependent mechanism. Therapy targeting this cathelicidin-regulating system might be beneficial in patients suffering from psoriasis.


Repairing and recovering broken peritoneal catheters.
Breakage of peritoneal catheters is an emergency of the technique that is uncommon but which requires immediate action when there is leakage of the dialysate and risk of infection. Early and adequate intervention can save broken catheters without interrupting peritoneal dialysis. We report our experience repairing damaged catheters using the Quinton® Peri-Patch repair kit (Quinton Instrument Co., Tyco Healthcare Group LP. Mansfield, MA., U.S.A.).


Cholesterol-based personal risk assessment in coronary heart disease.
Using data from the National Health and Nutrition Examination Survey (NHANES II) 1976-1980, we demonstrate how cross-sectional total serum cholesterol surveillance data can be used by an individual to assess current and future personal cholesterol risk status. We propose statistical models, based on a person's current measured cholesterol level and the relationship between cross-sectional age and cholesterol percentile estimates, that will allow prediction of future cholesterol levels or the age at which specified cholesterol risk levels will be reached if no cholesterol-altering intervention is taken. These models incorporate the observed variation in the NHANES II data and expected intraperson biological variation and intralaboratory analytical variation. We illustrate the adequacy of the models using data from the longitudinal Framingham Study.


Pre-post pilot study of noise levels at a university hospital center pharmacy department.
Noise interferes with attention, speech understanding, detection of other auditory stimuli, and leads to interruptions. This is a pre-post cross-sectional observational study aimed at measuring noise levels in a 500-bed mother-child university hospital center pharmacy department after the implementation of corrective measures, such as work zone reorganization, digitization of the prescription process, and education about the impact of some work habits. A total of 24 measurement points (70 noise level measurements) were taken in 2007 (pre) compared to 30 measurement points (59 noise level measurements) in 2012 (post). There was a statistically significant difference in the average values of the day and night noise measurements (day 59.4 ± 5.3 dB(A) vs night 52.3 ± 8.0 dB(A); P < .001). There were no statistically significant differences in the average values of the noise measurements taken during daytime between the prestudy and poststudy phases (pre 59.4 ± 5.3 vs post 58.07 ± 6.01 dB(A); P = .22). Few data exist on the noise levels in hospital pharmacy departments. In spite of the corrective measures implemented, reducing noise levels in pharmacy departments was difficult to achieve. Average values of approximately 60 dB(A) seem to be unacceptable for work that requires a high level of attention.


Immunity and the emergence of virulent pathogens.
The emergence/re-emergence of infectious diseases has been one of the major concerns for human and wildlife health. In spite of the medical and veterinary progresses as to prevent and cure infectious diseases, during the last decades we have witnessed the emergence/re-emergence of virulent pathogens that pose a threat to humans and wildlife. Many factors that might drive the emergence of these novel pathogens have been identified and several reviews have been published on this topic in the last years. Among the most cited and recognized drivers of pathogen emergence are climate change, habitat destruction, increased contact with reservoirs, etc. These factors mostly refer to environmental determinants of emergence. However, the immune system of the host is probably the most important environmental trait parasites have to cope with. Here, we wish to discuss how immune-mediated selection might affect the emergence/re-emergence of infectious diseases and drive the evolution of disease severity. Vaccination, natural (age-associated) and acquired immunodeficiencies, organ transplantation, environmental contamination with chemicals that disrupt immune functions form populations of hosts that might exert specific immune-mediated selection on a range of pathogens, shaping their virulence and evolution, and favoring their spread to other populations of hosts.


A fluorometric method for the differentiation of algal populations in vivo and in situ.
Fingerprints of excitation spectra of chlorophyll (Chl) fluorescence can be used to differentiate 'spectral groups' of microalgae in vivo and in situ in, for example, vertical profiles within a few seconds. The investigated spectral groups of algae (green group, Chlorophyta; blue, Cyanobacteria; brown, Heterokontophyta, Haptophyta, Dinophyta; mixed, Cryptophyta) are each characterised by a specific composition of photosynthetic antenna pigments and, consequently, by a specific excitation spectrum of the Chl fluorescence. Particularly relevant are Chl a, Chl c, phycocyanobilin, phycoerythrobilin, fucoxanthin and peridinin. A laboratory-based instrument and a submersible instrument were constructed containing light-emitting diodes to excite Chl fluorescence in five distinct wavelength ranges. Norm spectra were determined for the four spectral algal groups (several species per group). Using these norm spectra and the actual five-point excitation spectrum of a water sample, a separate estimate of the respective Chl concentration is rapidly obtained for each algal group. The results of dilution experiments are presented. In vivo and in situ measurements are compared with results obtained by HPLC analysis. Depth profiles of the distribution of spectral algal groups taken over a time period of few seconds are shown. The method for algae differentiation described here opens up new research areas, monitoring and supervision tasks related to photosynthetic primary production in aquatic environments.


Adaptive evolution of HIV at HLA epitopes is associated with ethnicity in Canada.
Host immune selection pressure influences the development of mutations that allow for HIV escape. Mutation patterns induced in HIV by the human leukocyte antigen (HLA) are HLA-allele specific. As ethnic groups have distinct and characteristic HLA allele frequencies, we can expect divergent viral evolution within ethnicities. Here, we have sequenced and analyzed the HIV pol gene from 1248 subtype B infected, treatment-naïve individuals in Canada. Phylogenetic analysis showed no separation between pol sequences from five self-identified ethnic groups, yet fixation index (F(ST)) values showed significant divergence between ethnicities. A total of 17 amino acid sites showed an ethnic-specific fixation pattern (0.015<F(ST) <0.060, p<0.01), and 27 codons were inferred to be under positive selection (p<0.01), with each set of sites strongly associated with HLA sites (p = 1.78×10(-6) and p = 1.91×10(-7), respectively). Within the pol gene, eight sites under HLA selective pressure were correlated with ethnicity, indicating 'adaptive divergence' between the groups studied. Our findings highlight challenges in HIV vaccine design in ethnically diverse countries with subtype B epidemics.


The Interface Between Iron Metabolism and Gene-Based Iron Contrast for MRI.
Using a gene-based approach to track cellular and molecular activity with magnetic resonance imaging (MRI) has many advantages. The strong correlation between transverse relaxation rates and total cellular iron content provides a basis for developing sensitive and quantitative detection of MRI reporter gene expression. In addition to biophysical concepts, general features of mammalian iron regulation add valuable context for interpreting molecular MRI predicated on gene-based iron labeling. With particular reference to the potential of magnetotactic bacterial gene expression as a magnetic resonance (MR) contrast agent for mammalian cell tracking, studies in different cell culture models highlight the influence of intrinsic iron regulation on the MRI signal. The interplay between dynamic regulation of mammalian iron metabolism and expression systems designed to sequester iron biominerals for MRI is presented from the perspective of their potential influence on MR image interpretation.


FEA modeling of CMUT with membrane stand-off structures to enable selectable frequency-mode operation.
A selectable, dual-frequency, capacitive micro- machined ultrasonic transducer (CMUT) designed for both high-frequency imaging and low-frequency therapeutic effect is presented. A validated finite element analysis (FEA) CMUT model was used to examine the performance of the proposed dual-frequency transducer. CMUT device simulations were used to design a hybrid device incorporating stand-off structures that divide a large, low-frequency membrane into smaller, high-frequency sub-membranes when the membrane is partially collapsed so that the stand-offs contact the substrate. In low-frequency operation, simulations indicated that the peak negative pressure achieved by the hybrid device, when biased by 30.0 VDC and excited by a 2-MHz signal with 30.0 V amplitude, exceeded 190 kPa, which is sufficient for microbubble rupture. Low-frequency mode bandwidth was 93% at a center frequency of 2.1 MHz. In the high-frequency mode of operation, the device was excited by 175 Vdc and 87.5 Vac, which generated a peak negative pressure of 247 kPa. Device center frequency was 44.1 MHz with a - 6-dB fractional bandwidth of 42%.


[Differential diagnostic aspects of lethal midline granulomas (granuloma gangraenescens].
The lethal midline granuloma and limited Wegener's granulomatosis show clinical similarity, although they are of different etiology. The following case of a 53-year-old woman shows how difficult it is to establish the precise diagnosis of lethal midline granuloma. The diagnosis depends on the pathological finding of a lymphoma. The lymphoma can be differentiated in a T- or a B-cell lymphoma by immunostaining. However, the diagnostic yield of biopsies from the nose is not perfect. It would be, therefore, important to find other diagnostic criteria. The presence of the c-ANCA is a helpful tool, but in the case of limited Wegener's granulomatosis, it has a sensitivity of 50%. The prognosis of the lethal midline granuloma is poor even if an adequate radiation therapy is instituted.


Whence river blindness? The domestication of mammals and host-parasite co-evolution in the nematode genus Onchocerca.
The genus Onchocerca includes 34 described species and represents one of the largest genera of the filarial nematodes within the family Onchocercidae. Representative members of this genus are mainly parasites of ungulates, with some exceptions such as Onchocerca lupi and Onchocerca volvulus, infecting carnivores and/or humans. For a long time, the evolutionary relationships amongst onchocercids remained poorly studied, as the systematics of this genus was impaired by the high morphological variability of species included in the taxon. Although some molecular phylogenies were developed, these studies were mainly focused on bovine Onchocerca spp. and O. volvulus, including assessments of Wolbachia endosymbionts. In the present study, we analysed 13 Onchocerca spp. from a larger host spectrum using a panel of seven different genes. Analysis of the coxI marker supports its usefulness for the identification of species within the genus. The evolutionary history of the genus has been herein revised by multi-gene phylogenies, presenting three strongly supported clades of Onchocerca spp. Analyses of co-evolutionary scenarios between Onchocerca and their vertebrate hosts underline the effect of domestication on Onchocerca speciation. Our study indicates that a host switch event occurred between Bovidae, Canidae and humans. Cophylogenetic analyses between Onchocerca and the endosymbiotic bacterium Wolbachia indicate the strongest co-evolutionary pattern ever registered within the filarial nematodes. Finally, this dataset indicates that the clade composed by O. lupi, Onchocerca gutturosa, Onchocerca lienalis, Onchocerca ochengi and O. volvulus derived from recent speciation.


Pulmonary involvement in brucellosis.
Brucellosis is a zoonotic disease caused by a Gram-negative bacillus of the Brucella genus with multisystem involvement, primarily affecting the reticuloendothelial system, joints, heart and kidneys. Although the disease can be spread by inhalation, pulmonary involvement is rare. To report a case of brucellosis with pulmonary involvement. CASE PRESENTAION: A previously healthy 36-year-old woman was admitted with complaints of fever, weakness, night sweats, dry cough and bilateral chest pain. She hed been diagnosed with pneumonia 20 days previously and was started on a course of ampicillin for 14 days, with no response. Her chest auscultation revealed diminished breath sounds and scattered crackles and rhonchi over the inferior zone of the right hemithorax. Wright and Coombs testing resulted in titres of 1:1280 and 1:640, respectively. Chest radiography revealed an area of confluent lobar consolidation in the right lower lobe. Treatment was started with a six-week course of oral doxycycline 200 mg/day and rifampicin 600 mg/day. This treatment regimen rapidly improved the patient's condition. Follow-up after one year showed no residual effects from the infection. Pulmonary involvement is a rare event in the course of brucellosis, but the rate could be higher than currently estimated. In endemic regions, brucellosis should be considered as a causative agent in patients with pulmonary symptoms. Brucellosis is a zoonotic disease caused by a Gram-negative bacillus of the Brucella genus with multisystem involvement, primarily affecting the reticuloendothelial system, joints, heart and kidneys. Although the disease can be spread by inhalation, pulmonary involvement is rare. To report a case of brucellosis with pulmonary involvement. A previously healthy 36-year-old woman was admitted with complaints of fever, weakness, night sweats, dry cough and bilateral chest pain. She hed been diagnosed with pneumonia 20 days previously and was started on a course of ampicillin for 14 days, with no response. Her chest auscultation revealed diminished breath sounds and scattered crackles and rhonchi over the inferior zone of the right hemithorax. Wright and Coombs testing resulted in titres of 1:1280 and 1:640, respectively. Chest radiography revealed an area of confluent lobar consolidation in the right lower lobe. Treatment was started with a six-week course of oral doxycycline 200 mg/day and rifampicin 600 mg/day. This treatment regimen rapidly improved the patient's condition. Follow-up after one year showed no residual effects from the infection. Pulmonary involvement is a rare event in the course of brucellosis, but the rate could be higher than currently estimated. In endemic regions, brucellosis should be considered as a causative agent in patients with pulmonary symptoms.


Opposing effects of Toll-like receptor stimulation induce autoimmunity or tolerance.
Toll-like receptor (TLR) activation by pathogens can induce the activation of diverse cell populations of the immune system and, therefore, can initiate or augment protective T-helper 1 immune responses. However, on a susceptible genetic background, TLR stimulation can also induce autoimmunity. The relative contribution of either microbe-derived or endogenous antigens, such as single-stranded RNA and unmethylated DNA, to TLR stimulation and the development of specific autoimmune diseases are still debated. Here, we review the different possibilities. Furthermore, tolerance induction by TLRs, which originally had been postulated to be protective by limiting excessive inflammation and, thus, preventing septic shock, has come into focus as a mechanism to control autoimmunity by inhibiting dendritic-cell maturation. In some murine models of systemic lupus erythematosus, TLR9 deficiency results in a shift from anti-nucleosome to TLR7-dependent anti-ribonucleoprotein IgG2a and IgG2b autoantibodies, and enhanced disease progression and mortality. Thus, not only can TLR signalling induce autoimmunity, but TLR(9) stimulation might also regulate tolerance.


Rubber and plastic ammunition lethal injuries: the Israeli experience.
Rubber and plastic ammunition was used by the Israeli Defence Forces between the years 1987 and 1993 (Intifada) almost exclusively as a deterrent to aggression by the Palestinian civilian population in the occupied territories of Gaza, Judea and Samaria. While designed to avoid the serious wounds and deaths caused by the use of conventional military ammunition, the firing of rubber and plastic bullets has resulted in extensive injuries and more than 20 deaths. The data from the autopsies of 17 of these victims, mostly teenagers, were analysed. Ten of the victims died from injuries inflicted by Improved Rubber Bullets, while the other seven succumbed to injuries caused by Plastic Bullets. In most instances, the cause of death was related to injuries to the brain. Ballistic features of non-conventional bullets are discussed, and suggestions to curtail the serious injuries and fatalities arising from their use are given, with emphasis on firing from a safe range. British and South African experience with this type of ammunition is compared with our observations.


In vivo colocalization of antigen and CpG [corrected] within dendritic cells is associated with the efficacy of cancer immunotherapy.
Immunostimulatory cytidyl guanosyl (CpG) motifs are of great interest as cancer vaccine adjuvants. They act as potent inducers of Th1 responses, including the activation of cytotoxic CD8(+) T lymphocytes (CTL). Whereas animal models have provided clear evidence that CpG enhances antitumor immunity, clinical trials in humans have thus far been less successful. Applying cryosurgery as an instant in situ tumor destruction technique, we now show that timing of CpG administration crucially affects colocalization of antigen and CpG within EEA-1(+) and LAMP-1(+) compartments within dendritic cells in vivo. Moreover, antigen/CpG colocalization is directly correlated with antigen cross-presentation, the presence of CTL, and protective antitumor immunity. Thus, failure or success of CpG as a vaccine adjuvant may depend on colocalization of antigen/CpG inside DCs and hence on the timing of CpG administration. These data might aid in the design of future immunotherapeutic strategies for cancer patients.


Turning an aptamer into a light-switch probe with a single bioconjugation.
We describe a method for transforming a structure-switching aptamer into a luminescent light-switch probe via a single conjugation. The methodology is demonstrated using a known aptamer for Hg(2+) as a case study. This approach utilizes a lanthanide-based metallointercalator, Eu-DOTA-Phen, whose luminescence is quenched almost entirely and selectively by purines, but not at all by pyrimidines. This complex, therefore, does not luminesce while intercalated in dsDNA, but it is bright red when conjugated to a ssDNA that is terminated by several pyrimidines. In its design, the light-switch probe incorporates a structure-switching aptamer partially hybridized to its complementary strand. The lanthanide complex is conjugated to either strand via a stable amide bond. Binding of the analyte by the structure-switching aptamer releases the complementary strand. This release precludes intercalation of the intercalator in dsDNA, which switches on its luminescence. The resulting probe turns on 21-fold upon binding to its analyte. Moreover, the structure switching aptamer is highly selective, and the long luminescence lifetime of the probe readily enables time-gating experiments for removal of the background autofluorescence of the sample.


Design, development and evaluation of novel nanoemulsion formulations for transdermal potential of celecoxib.
The aim of the present study was to investigate the potential of nanoemulsion formulations for transdermal delivery of celecoxib (CXB). The in vitro skin permeation profile of optimized formulations was compared with CXB gel and nanoemulsion gel. Significant increase in the steady state flux (Jss), permeability coefficient (Kp) and enhancement ratio (Er) was observed in nanoemulsion formulations T1 and T2 (p < 0.05). The highest value of these permeability parameters was obtained in formulation T2, which consisted of 2% (m/m) of CXB, 10% (m/m) of oil phase (Sefsol 218 and Triacetin), 50% (m/m) of surfactant mixture (Tween-80 and Transcutol-P) and 40% (m/m) water. The anti-inflammatory effects of formulation T2 showed a significant increase (p < 0.05) in inhibition after 24 h compared to CXB gel and nanoemulsion gel on carrageenan-induced paw edema in rats. These results suggested that nanoemulsions are potential vehicles for improved transdermal delivery of CXB.


HPV testing can reduce the number of follow-up visits in women treated for cervical intraepithelial neoplasia grade 3.
We evaluated high-risk human papillomavirus (HPV) testing by Hybrid Capture II (HC II) in addition to cytology to predict recurrent/residual cervical intraepithelial neoplasia (CIN) 2/3 and cervical cancer in women treated for CIN 3. Follow-up study of 108 women with histologically confirmed CIN 3. Pretreatment, in 96% (104/108) of the smears high-risk HPV DNA was present. Posttreatment, 71% (77/108) of the women had normal cytology and negative HC II test and none developed recurrent/residual disease during a median follow-up of 28.8 months with a range of 2.4-64.8 months. One of the 12% (13/108) of women with normal cytology and positive HC II test was diagnosed with cervical adenocarcinoma. One of the 7% (8/108) of women with abnormal cytology (borderline dyskaryosis or worse) and negative HC II test was diagnosed with CIN 2. Three of the 9% (10/108) of women with abnormal cytology and a positive HC II test were diagnosed with CIN 2/3. These results show an increased risk for recurrent/residual CIN 2/3 and cervical carcinoma when at least one posttreatment test is positive. The highest relative risk (72.9, 95% CI 25-210) was present in women with both tests positive. HPV testing with Hybrid Capture II in conjunction with cytology can be used as a tool to select women with an increased risk for recurrent/residual CIN 2/3 and cervical cancer. The standard policy in The Netherlands is cytology at 6, 12, and 24 months posttreatment. However, for women with both normal cytology and negative HC II test at 6 months the chance to develop recurrent/residual CIN 2/3 and cervical carcinoma is so low that retesting at 12 months can be omitted.


Kinesins relocalize the chromosomal passenger complex to the midzone for spindle disassembly.
Mitotic spindle disassembly after chromosome separation is as important as spindle assembly, yet the molecular mechanisms for spindle disassembly are unclear. In this study, we investigated how the chromosomal passenger complex (CPC), which contains the Aurora B kinase Ipl1, swiftly concentrates at the spindle midzone in late anaphase, and we researched the role of this dramatic relocalization during spindle disassembly. We showed that the kinesins Kip1 and Kip3 are essential for CPC relocalization. In cells lacking Kip1 and Kip3, spindle disassembly is severely delayed until after contraction of the cytokinetic ring. Purified Kip1 and Kip3 interact directly with the CPC and recruit it to microtubules in vitro, and single-molecule experiments showed that the CPC diffuses dynamically on microtubules but that diffusion stops when the CPC encounters a Kip1 molecule. We propose that Kip1 and Kip3 trap the CPC at the spindle midzone in late anaphase to ensure timely spindle disassembly.


Coupling of gel-based 2-DE and 1-DE shotgun proteomics approaches to dig deep into the leaf senescence proteome of Glycine max.
Leaf senescence is the last stage of leaf development that re-mobilizes nutrients from the source to sink. Here, we have utilized the soybean as a model system to unravel senescence-associated proteins (SAPs). A comparative proteomics approach was used at two contrasting stages of leaf development, namely mature (R3) and senescent (R7). Selection criteria for these two stages were the contrasting differences in their biochemical parameters - chlorophyll, carotenoids and malondialdehyde contents. Proteome analysis involved subjecting the total leaf proteins to 15% poly-ethylene glycol (PEG) pre-fractional method to enrich the low-abundance proteins (LAPs) and their analyses by gel-based 2-DE and 1-DE shotgun proteomics approaches. 2-DE profiling of PEG-supernatant and -pellet fractions detected 153 differential spots between R3 and R7 stages, of which 102 proteins were identified. In parallel, 1-DE shotgun proteomics approach identified 598 and 534 proteins in supernatant and pellet fractions of R3 and R7 stages, respectively. MapMan and Gene Ontology analyses showed increased abundance and/or specific accumulation of proteins related to jasmonic acid biosynthesis and defense, while proteins associated with photosynthesis and ROS-detoxification were decreased during leaf senescence. These findings and the generated datasets further our understanding on leaf senescence at protein level, providing a resource for the scientific community. Leaf senescence is a major biological event in the life cycle of plants that leads to the recycling of nutrients. However, the molecular mechanisms underlying leaf senescence still remain poorly understood. Here, we used a combination of gel-based 2-DE and 1-DE shotgun proteomics approaches to dig deeper into the leaf senescence proteome using soybean leaf as a model experimental material. For the identification of low-abundance proteins, polyethylene glycol (PEG) fractionation was employed and both PEG-supernatant and -pellet fractions were utilized for 2-DE and shotgun proteomic analysis. A total of 1234 (102 from 2-DE and 1132 from 1-DE shotgun proteome analysis) proteins were identified which were functionally annotated using GO and MapMan bioinformatics tools. Our results also emphasize the role of jasmonic acid in soybean leaf senescence.


Diminishing benefit of smoking cessation medications during the first year: a meta-analysis of randomized controlled trials.
Although smoking cessation medications have shown effectiveness in increasing abstinence in randomized controlled trials (RCTs), it is unclear to what extent benefits persist over time. This paper assesses whether the benefits of smoking cessation medications decline over the first year. We selected studies from three systematic reviews published by the Cochrane Collaboration. RCTs of first-line smoking cessation medications, with 6- and 12-month follow-up, were eligible for inclusion. Meta-analysis was used to synthesize information on sustained abstinence (SA) at 6 versus 12 months and 3 versus 6 months, using the risk difference (RD) ('net benefit') between intervention and control group quit rates, the relative risk (RR) and the odds ratio (OR). Sixty-one studies (27 647 participants) were included. Fewer than 40% of intervention group participants were sustained abstinent at 3 months (bupropion: 37.1%; nicotine replacement therapy (NRT): 34.8%; varenicline: 39.3%); approximately a quarter were sustained abstinent at 6 months (bupropion: 25.9%; NRT: 26.6%; varenicline: 25.4%), and approximately a fifth were sustained abstinent at 12 months (bupropion: 19.9%; NRT: 19.8%%; varenicline: 18.7%). There was only a small decline in RR (3 months: 1.95 [95% confidence interval (CI) = 1.74-2.18, P < 0.0001]; 6 months: 1.87 (95% CI = 1.67-2.08 P < 0.0001); 12 months: 1.75 (95% CI = 1.56-1.95, P < 0.0001) between intervention and control groups over time, but a substantial decline in net benefit [3 months: RD = 17.3% (14.5-20.1%); 6 months: RD = 11.8% (10.0-13.7%); 12 months: RD = 8.2% (6.8-9.6%)]. The decline in net benefit was statistically significant between 3 and 6 [RD = 4.95% (95% CI = 3.49-6.41%), P < 0.0001] and 6 and 12 months [RD = 3.00% (95% CI = 2.36%-3.64%), P < 0.0001)] for medications combined and individual medications. The proportion of smokers who use smoking cessation medications who benefit from doing so decreases during the course of the first year, but a net benefit still remains at 12 months.


The role of 5-hydroxytryptamine in the feline response to intravenous infusion of live E. coli.
A standardized septic shock was induced in cats by intravenous infusion of a live E. coli bacteria strain. The bacterial infusion induced a rapid haemodynamic response characterized mainly by a pulmonary arterial hypertension and a late phase characterized by systemic hypotension and hypodynamic circulation. Systemic arterial, pulmonary arterial, portal venous, left atrial pressures, max inspiratory-expiratory pressure difference in the trachea, aortic and intestinal blood flows were monitored. Arterial blood samples were taken for recording the number of circulating platelets and white blood cells and for determining the acid-base balance. The effect of pretreatment with ketanserin, a specific 5-hydroxytryptamine2 (5-HT2)-receptor blocker on these haemodynamic reactions was studied. In short term experiments on non-bacteriaemic control cats, ketanserin prevented the pulmonary hypertension induced by intravenous 5-HT infusions but not the increase in intestinal blood flow. Ketanserin induced a reduction of total peripheral (including intestinal) vascular resistance to blood flow but had no effect on aortic blood flow. After infusion of bacteria, ketanserin pretreated cats were more hypotensive due to a relative peripheral dilatation of the resistance vessels. Ketanserin pretreatment had no effect on the pulmonary vascular reactions, the tracheal pressure difference or the number of circulating platelets or white blood cells. Thus, except for a more pronounced hypotension early after bacterial infusion, ketanserin pretreatment did not influence the haemodynamic response. It is concluded that 5-HT is not of significant importance in the pathogenesis of the haemodynamic reactions following experimental bacteraemia.


Cortisol binding in plasma of men with unipolar and bipolar affective disorders.
Following an earlier report, plasma cortisol-binding capacity (CBC) was estimated in a new series of 11 men with unipolar depression and 11 men with bipolar illness admitted to hospital. The two groups were comparable except that the bipolar group tended to have more frequent episodes of illness and to have more family histories of affective disorder. There was no significant difference between the CBC values in each group.


Millisecond two-photon optical ribbon imaging for small-animal functional connectome study.
We developed a high-speed two-photon optical ribbon imaging system, which combines galvo-mirrors for an arbitrary curve scan on a lateral plane and a tunable acoustic gradient-index lens for a 100 kHz-1 MHz axial scan. The system provides micrometer/millisecond spatiotemporal resolutions, which enable continuous readout of functional dynamics from small and densely packed neurons in a living adult Drosophila brain. Compared to sparse sampling techniques, the ribbon imaging modality avoids motion artifacts. Combined with a Drosophila anatomical connectome database, which is the most complete among all model animals, this technique paves the way toward establishing whole-brain functional connectome.


Immunoperoxidase studies by monoclonal antibody B72.3 applied to breast aspirates: diagnostic considerations.
The purpose of this study was to determine the reactivity of monoclonal antibody (MAb) B72.3 when applied directly to aspiration biopsy cytology (ABC) of the breast in the following conditions: (1) infiltration lobular carcinoma; (2) fibrocystic disease; (3) fibroadenoma; and (4) apocrine cysts. Nine of ten aspirates from infiltrating lobular carcinoma were positive in these assays, while 21 of 22 benign cases reacted negatively. The single false-positive benign aspirate manifested a staining pattern characteristic of apocrine cells. This study demonstrates that the MAb B72.3 can be employed as a potentially valuable diagnostic adjunct. It can be used on stained aspirates to assist in the interpretation of ABC from breast lesions.


Construction and analyses of the microRNA-target gene differential regulatory network in thyroid carcinoma.
Thyroid-carcinoma (THCA) is the most common malignancy with an increasing incidence. Recent evidence has emphasized the role of microRNA (miRNA) in THCA. However, knowledge concerning the roles of miRNAs in THCA is still limited. We therefore use a miRNA-target gene differential regulatory network (MGDRN) to identify key miRNAs and characterize their synergistic regulation in THCA. Both miRNA-target gene interactions from multiple databases and negative expression correlations between miRNA-target genes were used to characterize the interactions. Then, two regulatory networks involving normal and tumor conditions were constructed, respectively. The MGDRN was finally constructed using different interactions between the above two regulatory networks. By analyzing topological features of the MGDRN, four miRNAs (hsa-mir-152-3p, hsa-mir-148a, hsa-mir-130b and hsa-mir-15b) are identified as key miRNAs in THCA. Over-expression of mir-152-3p inhibited proliferation and colony formation of TPC-1 cells. Furthermore, mir-152-3p negatively regulated ERBB3 by binding to the 3'-UTR of ERBB3, and down-regulation of ERBB3 by small interfering (si)RNAs inhibited proliferation and colony formation of TPC-1 cells, indicating that mir-152-3p acted as an anti-tumor miRNA by negatively regulating ERBB3. Finally, two synergistically dysregulated modules were identified which may contribute to the initiation and progression of THCA. Overall, the results provided a better understanding of the molecular basis of THCA, and suggested novel treatment strategies for this cancer.


Effects of balance evaluation comparison of dynamic balance and Y balance.
This study measured balance ability using both an existing clinical test tool, the Y-balance test (YBT), and an automated version of the YBT named the dynamic balance test (DBT) developed in this study. Correlations between the two methods were examined to determine whether the DBT can be used as an objective tool for balance ability evaluation. The subjects included in the study were 32 healthy male adults in their 20s, who were randomized into two groups, YBT and DBT, to compare the balance ability between the two groups. The maximum stretching distances of both legs in the anterior (AT), posteromedial (PM), and posterolateral (PL) directions were measured. Furthermore, to compensate for the difference in length between left and right legs, the mean and standard deviations were determined using the standardization formula, and the standardized values were represented as percentages. For the statistical analysis of the data, an independent t-test was performed using SPSS ver. 18.0. The test results showed no significant differences between the two groups in both left and right legs in the AT, PM, and PL directions (P>0.05). Therefore, measuring balance ability with the DBT, which uses digital sensor measurement technology (an automated data recording, wireless data transmission, storage, and management system; measurement is possible even by one subject of balance ability test), was found to be advantageous in respect to the YBT in terms of time, efficiency, and convenience.


Advances in research of the artificial cultivation of Ophiocordyceps sinensis in China.
Ophiocordyceps sinensis (syn. Cordyceps sinensis), a traditional Chinese medicine called DongChongXiaCao (DCXC) in Chinese, is well known and has been used in Asia countries since the fifteenth century, and it contains some valuable medicinal component defined by modern pharmacological science. DCXC only appears at high altitudes on the Qinghai-Tibetan Plateau. Consequently, it is difficult to find and harvest. Because of its rarity and medicinal value, DCXC has always been one of the most expensive medicines known. As the price of DCXC has risen in recent years, thousands of migrants have entered into the various grasslands to search for them in season, which makes ecological environments of the grassland more fragile. In order to relieve the environmental pressures and protect this valuable resource, the artificial cultivation of DCXC involving two aspects of the genus Hepialus and the fungi of the host larvae should be employed and applied at the first available time point. In this article, the reproduction of moth larvae of the genus Hepialus is first described, which includes their ecological characteristics and the methods of artificial feeding. Second, the generation and isolation method of the fungi from DCXC are subsequently summarized, and then the mechanism of fungal spores to attack the moth larvae are restated. Finally, the basic model of artificial cultivation of DCXC is introduced; meanwhile, the potential application of modern biotechnology to the artificial cultivation is analyzed in prospect. This review article will not only expand people's knowledge regarding the artificial cultivation of DCXC, but also hopefully provide an informative reference for the development of this valuable resource and the environmental protection of alpine meadows.


How does magnetic resonance compare with computed tomography?
Magnetic resonance (MR) is a new technology that has benefited by transfer of technology already developed for computed tomography (CT), but many further changes should be expected in its technologic development. Already MR imaging in some instances equals or surpasses CT, and other less obvious advantages may become apparent. MR costs may not compare unfavorably with those of CT, and increased cost might still be justified if more information can be obtained or if the need for other tests or length of hospitalization could be reduced. The fact that MR at this stage might equal CT is a real accomplishment; this performance should be acknowledged and rapid development and scientific investigation of MR technology should be actively supported.


Decline in incidence of endometrial cancer following increase in prescriptions for opposed conjugated estrogens in a prepaid health plan.
During the 1980s, the ecologic association of conjugated estrogens with endometrial cancer changed from positive to negative in a prepaid health plan. During the same period, use of progestins increased dramatically. We investigated whether the latter increase could explain the reversal of the estrogen-cancer association. Endometrial cancer incidence was estimated from cases recorded in the health plan registry divided by the number of women over age 45 years. Conjugated estrogens usage was measured as milligrams prescribed per woman per year and progestin was measured as tablets per woman per year, both based upon pharmacy records. Graphical and regression methods were used to analyze the resulting ecologic data. In a log-linear regression of incidence on conjugated estrogens and medroxyprogesterone usage, estrogen usage had a strong positive association with incidence, while medroxyprogesterone had a strong negative association with incidence. The change in the direction of the ecologic association between estrogen and endometrial cancer that occurred in 1984 continued until 1993, suggesting that the decline in endometrial cancer incidence and concomitant increase in conjugated estrogens usage since 1984 is explained by the increasing use of progestins. The data are entirely consistent with the hypothesis that progestins can protect against most of the excess risk conferred by conjugated estrogens, although the ecologic nature of the data prohibits drawing further inferences.


Drivers and applications of integrated clean-up technologies for surfactant-enhanced remediation of environments contaminated with polycyclic aromatic hydrocarbons (PAHs).
Surfactant-enhanced remediation (SER) is considered as a promising and efficient remediation approach. This review summarizes and discusses main drivers on the application of SER in removing polycyclic aromatic hydrocarbons (PAHs) from contaminated soil and water. The effect of PAH-PAH interactions on SER efficiency is, for the first time, illustrated in an SER review. Interactions between mixed PAHs could enhance, decrease, or have no impact on surfactants' solubilization power towards PAHs, thus affecting the optimal usage of surfactants for SER. Although SER can transfer PAHs from soil/non-aqueous phase liquids to the aqueous phase, the harmful impact of PAHs still exists. To decrease the level of PAHs in SER solutions, a series of SER-based integrated cleanup technologies have been developed including surfactant-enhanced bioremediation (SEBR), surfactant-enhanced phytoremediation (SEPR) and SER-advanced oxidation processes (SER-AOPs). In this review, the general considerations and corresponding applications of the integrated cleanup technologies are summarized and discussed. Compared with SER-AOPs, SEBR and SEPR need less operation cost, yet require more treatment time. To successfully achieve the field application of surfactant-based technologies, massive production of the cost-effective green surfactants (i.e. biosurfactants) and comprehensive evaluation of the drivers and the global cost of SER-based cleanup technologies need to be performed in the future.


[Use of urokinase in acute myocardial infarction].
Clinical course of the disease and the formation of the necrotic focus (as evidenced by precordial mapping from 35 ECG leads) were assessed in 88 patients with acute myocardial infarction, treated with 1,000,000 IU urokinase, in comparison to 41 untreated control patients. Thrombolytic therapy, started within the first 6 hours of myocardial infarction, was associated with a better clinical course of the disease. Urokinase administration after 6 hours from the onset of the symptoms produced no clinical improvement, did not limit the necrotic focus and failed to reduce mortality, as compared to the controls. The assessment of the efficiency of thrombolytic treatment demonstrated an at least 30% increment of venous flow in 45% of patients. Intravenous urokinase administration was accompanied by an activation of blood fibrinolytic system, and there was a tendency to fibrinolysis depression on the day following the administration.


New Correlation for Calculating Water Saturation Based on Permeability, Porosity, and Resistivity Index in Carbonate Reservoirs.
Water saturation assessment is recognized as one of the most critical aspects of formation evaluation, reserve estimation, and prediction of the production performance of any hydrocarbon reservoir. Water saturation measurement in a core laboratory is a time-consuming and expensive task. Many scientists have attempted to estimate water saturation accurately using well-logging data, which provides a continuous record without information loss. As a result, numerous models have been developed to relate reservoir characteristics with water saturation. By expanding the use and advancement of soft computing approaches in engineering challenges, petroleum engineers applied them to estimate the petrophysical parameters of the reservoir. In this paper, two techniques are developed to estimate the water saturation in terms of porosity, permeability, and formation resistivity index through the use of 383 data sets obtained from carbonate core samples. These techniques are the nonlinear multiple regression (NLMR) technique and the artificial neural network (ANN) technique. The proposed ANN model achieved outstanding performance and better accuracy for calculating the water saturation than the empirical correlation using NLMR and Archie equation with a high coefficient of determination (R 2) of 0.99, a low average relative error of 1.92, a low average absolute relative error of 13.62, and a low root mean square error of 0.066. To the best of our knowledge, the current research establishes a novel foundation using the ANN model in the estimation of water saturation.


Collateral circulation to an ischemic kidney.
A review of 301 consecutive abdominal arteriograms given to patients suspected of having occlusive arterial diseases was conducted. In 99 patients, 35% or more stenosis of the renal artery was demonstrated; of these, 40 showed demonstrable collaterals to the ischemic kidney. The adrenal and lumbar arteries contributed four times more frequently than the periureteric arteries to the collateral circulation. Characteristic ureteral notching from the periureteric artery collateral was noted in only 50% of the cases. Intrarenal collaterals were observed and appeared to contribute to the preservation of the size and function of the affected kidney.


Investigating the link between drug-naive first episode psychoses (FEPs), weight gain abnormalities and brain structural damages: Relevance and implications for therapy.
Evidence suggests that obesity and overweight may be associated with severe brain structural abnormalities and poor cognitive and functional outcomes in the general population. Despite these observations and the high prevalence of weight gain abnormalities in patients with psychosis spectrum disorders (PSDs), no studies have investigated the impact that these metabolic disturbances may have on brain structures and development in the earliest stages of PSDs. In the present review we shed light on the association between weight gain and brain structural abnormalities that may affect the course of illness in drug-naïve FEPs. Given the lack of studies directly investigating this issue, we firstly identified and critically evaluated the literature assessing weight gain abnormalities and gray or white matter (GM, WM) volumes (either globally or in specific regions of interest) in otherwise healthy obese/overweight adolescents and young adults. We then compared the results of this systematic review with those of two recent meta-analysis investigating GM and WM abnormalities in drug-naïve FEPs. Weight gain in otherwise healthy subjects was consistently associated with frontal and temporal GM atrophy and with reduced integrity of WM in the corpus callosum. Of relevance, all these brain regions are affected in drug-naïve FEPs, and their integrity is associated with clinical, cognitive and functional outcomes. The underlying mechanisms that may explain the association between weight gain, adiposity, and brain damage in both healthy subjects and drug-naïve FEPs are widely discussed. On the basis of this knowledge, we tried: a) to deduce an integrative model for the development of obesity in psychosis spectrum disorders; b) to identify the key vulnerability factors underlying the association between weight gain and psychosis; c) to provide information on new potential targets of intervention.


STOP-Bang Score and Prediction of Severity of Obstructive Sleep Apnea in a First Nation Community in Saskatchewan, Canada.
The STOP-Bang questionnaire is an easy-to-administer scoring model to screen and identify patients at high risk of obstructive sleep apnea (OSA). However, its diagnostic utility has never been tested with First Nation peoples. The objective was to determine the predictive parameters and the utility of the STOP-Bang questionnaire as an OSA screening tool in a First Nation community in Saskatchewan. The baseline survey of the First Nations Sleep Health Project (FNSHP) was completed between 2018 and 2019. Of the available 233 sleep apnea tests, 215 participants completed the STOP-Bang score questionnaire. A proportional odds ordinal logistic regression analysis was conducted using the total score of the STOP-Bang as the independent variable with equal weight given to each response. Predicted probabilities for each score at cut-off points of the Apnea Hypopnea Index (AHI) were calculated and plotted. To assess the performance of the STOP-Bang questionnaire, sensitivity, specificity, positive predictive values (PPVs), negative predictive values (NPVs), and area under the curve (AUC) were calculated. These data suggest that a STOP-Bang score ≥ 5 will allow healthcare professionals to identify individuals with an increased probability of moderate-to-severe OSA, with high specificity (93.7%) and NPV (91.8%). For the STOP-Bang score cut-off ≥ 3, the sensitivity was 53.1% for all OSA and 72.0% for moderate-to-severe OSA. For the STOP-Bang score cut-off ≥ 3, the specificity was 68.4% for all OSA and 62.6% for moderate-to-severe OSA. The STOP-Bang score was modestly superior to the symptom of loud snoring, or loud snoring plus obesity in this population. Analysis by sex suggested that a STOP-Bang score ≥ 5 was able to identify individuals with increased probability of moderate-to-severe OSA, for males with acceptable diagnostic test accuracy for detecting participants with OSA, but there was no diagnostic test accuracy for females.


New MSC: MSCs as pericytes are Sentinels and gatekeepers.
Human Mesenchymal Stem Cells, hMSCs, were first named over 25 years ago with the "stem cell" nomenclature derived from the fact that we and others could cause these cells to differentiate into a number of different mesodermal phenotypes in cell culture. The capacity to form skeletal tissue in vitro encouraged the use of hMSCs for the fabrication of tissue engineered skeletal repair tissue with subsequent transplantation to in vivo sites. With the current realization that MSCs are derived from perivascular cells, pericytes, and the immunomodulatory and trophic capabilities of MSCs in both in vitro and in vivo test systems, a complete re-evaluation of the role and functions of MSCs in the body was required. Additionally, the skeleton is a preferred organ for cancer dissemination from various tumor malignancies. To date, most efforts to understand skeletal metastasis have focused on the invasive and digestive capability of disseminated tumor cells (DTCs). The contribution of the target organ-specific microvascular structure influencing extravasation is less well understood. Current targeted cancer therapies are designed to alter not only biological functions in DTCs, but also components of the tumor stroma/microenvironment such as blood vessels. We now have a comprehensive image of the critical role of the host vasculature as an instructive niche for DTCs. The focus of this manuscript is to present the current information about MSC function in situ and to emphasize how these new observations provide insight into understanding the role of the pericyte/MSC in skeletal activities including our new hypothesis for how these cells act as a gatekeeper for metastasis of melanoma into bone. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1151-1159, 2017.


The Application of Stem Cells from Different Tissues to Cartilage Repair.
The degeneration of articular cartilage represents an ongoing challenge at the clinical and basic level. Tissue engineering and regenerative medicine using stem/progenitor cells have emerged as valid alternatives to classical reparative techniques. This review offers a brief introduction and overview of the field, highlighting a number of tissue sources for stem/progenitor cell populations. Emphasis is given to recent developments in both clinical and basic sciences. The relative strengths and weaknesses of each tissue type are discussed.


Reaching the homebound elderly: the Prescription Intervention and Lifelong Learning (PILL) program.
This article describes the Prescription Intervention and Lifelong Learning (PILL) program, a three-year pilot project to develop in-home pharmacy care services to clients of a community-based social service agency. Clients who were homebound, at least 62 years of age, and taking at least five medications were eligible for inclusion. Potential participants were referred by care managers to the pharmacist, who conducted an in-home evaluation of the medication regimen and assessed the risk for medication-related problems. The pharmacist provided instruction for hypertension and diabetes mellitus self-monitoring, extensive medication counseling for clients with complex medications regimens, and conducted other activities to promote positive medication- related outcomes. The clients served were primarily female, between 70 and 90 years of age, and almost one-half lived alone. They were taking an average of more than nine medications daily, and had at least one chronic disease. The clients of the social service agency were highly vulnerable to medication-related problems and were in need of in-home pharmacy care services.


Determination of the Main Phase Transition Temperature of Phospholipids by Oscillatory Rheology.
Knowledge of the physical and chemical properties of phospholipids, such as phase transition temperatures (Tc), is of great importance in order to reveal the functionalities of biological and artificial membranes. Our research group developed an oscillatory rheological method for the simple and rapid determination of phase transition temperatures (Tc). The phospholipids constructing the membranes undergo conformational changes at their Tc, which cause alterations of viscoelastic properties of the molecules. The oscillatory technique recommended by us proved to be appropriate to reveal the altered molecular properties of phospholipids as tracking the slightest changes in the viscoelasticity. Our study demonstrates the abrupt changes in rheological properties at Tc for the following phospholipids: 1,2-Dimyristoyl-sn-glycero-3-Phosphocholine (DMPC), 1,2-Dipalmitoyl-sn-glycero-3-Phosphatidylcholine (DPPC), and 1,2-Distearoyl-sn-glycero-3-Phosphocholine (DSPC), proving that the applied methodology is adequate for determining the Tc of phospholipids.


[Atrial arrhythmias after surgical repair of an atrial septal defect (secundum-type). Six years follow-up in adults (author's transl)].
Atrial arrhythmias before and after repair of an atrial septal defect (secundum-type) were analyzed in 100 patients. The mean postoperative follow-up was 5.8 years, the mean age at the last check-up was 33.4 years. Preoperatively, 10 patients showed atrial arrhythmias (6 pts atrial flutter or fibrillation [AF], 3 pts sinus node [SN] dysfunction, 1 pt atrial tachycardia). About 6 years after operation, 29 patients showed atrial arrhythmias (16 pts AF, 10 pts SN dysfunction, 3 pts atrial tachycardias). The 26 patients with AF and SN dysfunction were 10 years older and had a 3 years longer follow-up period postoperatively than those with sinus rhythm. In addition, they had a higher pulmonary artery pressure preoperatively. Especially the occurrence of AF after operation was strongly related to the age and the pulmonary artery pressure. All other factors had no significance. The data show that closure of an atrial septal defect cannot prevent the occurrence of AF in the following period. In addition, SN dysfunction is found postoperatively in a significant number of patients probably due to the intraoperative injury to the sinus node. However, it cannot be excluded that the unfavorable results may in part be due to the selection of the patients.


Study on Lactiplantibacillus plantarum R6-3 from Sayram Ketteki to prevent chronic unpredictable mild stress-induced depression in mice through the microbiota-gut-brain axis.
The prevention, mitigation and treatment of depression has become a global issue that needs to be solved urgently. Sayram Ketteki, a traditional natural fermented yoghurt from the region with the world's fourth highest life expectancy, has been known as the "longevity secret", whose longevity and anti-depression factors are speculated to come from its rich microorganisms. Therefore, for the first time, we systematically studied in depth the microbes of Sayram Ketteki, screened a new edible probiotic strain, Lactiplantibacillus plantarum R6-3, and explored its anti-depression effect in chronic unpredictable mild stress (CUMS)-induced depression in mice. It is encouraging that L. plantarum R6-3 was significantly superior to the classic anti-depressant drug, fluoxetine, in the performance of promoting sucrose preference test (SPT) behavior by 18% (p < 0.001), lowering the serum CORT content by 5.6% (p < 0.05), accelerating the brain-derived neurotrophic factor (BDNF) level by 5.9% (p < 0.01), increasing the serum IL-10 concentration by 2.3% (p < 0.05), up-regulating the expression of BDNF and phosphorylated-ERK by 74% (p < 0.01) and 45% (p < 0.001), respectively, and facilitating the secretion of fecal short-chain fatty acids (SCFAs), including n-butyric, n-valeric, and isovaleric acid by 47% (p < 0.01), 42% (p < 0.05) and 38% (p < 0.05), respectively. Through the microbiota-gut-brain axis, L. plantarum R6-3 promoted the secretion of intestinal SCFAs through regulation of the composition and function of the gut microbiota, and activated the production of the monoamine neurotransmitter, renewed the level of brain neurotrophic factor, and suppressed the hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis by adjusting the hippocampal BDNF/TrkB/ERK/CREB signaling pathway, thereby improving the immune and oxidative stress status, protecting hippocampal tissue from damage, maintaining a healthy weight and preventing CUMS-induced depressive behavior in mice. It has great prospects for the development of natural functional foods, the prevention and treatment of depression and in innovative microecological preparations.


An Unusual Presentation of Occult Small-Cell Neuroendocrine Carcinoma as Acalculous Cholecystitis With Widespread Liver Metastasis.
Small-cell neuroendocrine carcinoma, often classified as small-cell lung carcinoma (SCLC) type, is an aggressive neuroendocrine tumor with early metastatic potential that can lead to unexpected patient presentations. We report the case of a 69-year-old man who presented to the emergency department with worsening right upper abdominal pain, nausea, and vomiting for the past several days. The clinical picture and the workup, including the complete metabolic panel and complete blood count, were highly suggestive of acute cholecystitis with transaminitis and direct hyperbilirubinemia. The ultrasound and magnetic resonance cholangiopancreatography of the abdomen revealed a diffusely hyperdense and hypertrophic liver without evidence of choledocholithiasis. After initial resuscitation, the patient underwent laparoscopic cholecystectomy. Intraoperative findings were consistent with diffuse miliary liver metastatic disease of unknown etiology, rigid liver parenchyma, an extremely frail gallbladder wall, and mild ascites. A biopsy of the liver and cholecystectomy were performed. The final pathology revealed metastatic SCLC to the liver and widespread intravascular tumor emboli, causing diffuse ischemia of the entire gallbladder wall. The patient's postoperative course was marked by the development of foudroyant liver insufficiency and worsening severe type B lactic acidosis.


Magnetic resonance imaging characteristics of ischemic brain infarction over time in a canine stroke model.
This study describes magnetic resonance imaging (MRI) results and changes in lateral ventricular size over time in a canine ischemic stroke model. T1- and T2-weighted (T1W, T2W) imaging and fluid-attenuated inversion recovery (FLAIR) sequence MRI were performed at 3 h and 3, 8, and 35 days after brain infarct induction. Diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) mapping were performed at 8 and 35 days. A total of 29 brain lesions were induced successfully in 12 of 14 beagle dogs. At 3 h, T2W and FLAIR detected hyperintense lesions in three randomly selected dogs. On T1W, all lesions appeared hypointense to isointense at 3 h, isointense (18/29) or hypointense (11/29) at 3 days, hypointense to isointense with peripheral hyperintensity (24/26) at 8 days, and hypointense (18/26) at 35 days. Infarcts on DWI/ADC were hypointense to isointense centrally, with the periphery hyperintense/hyperintense (17/26) at 8 days and hypointense/hyperintense (19/26) at 35 days. A marked increase in lateral ventricular size was observed in dogs with cerebral infarcts. In conclusion, T2W and FLAIR were useful for detecting early stage (3 h to 3 days) brain infarction. T1W and DWI were useful for detecting neuronal necrosis and providing supplemental information for phase evaluation.


Ribonucleic acid and other polyanions facilitate chromatin assembly in vitro.
Crude extracts of Drosophila embryos are a rich source of both DNA topoisomerase I and chromatin assembly activity [Nelson, T., Hsieh, T., & Brutlag, D.L. (1979) Proc. Natl. Acad. Sci. U.S.A. 76, 5510-5514; Hseih, T., & Brutlag, D. L. (1980) Cell (Cambridge, Mass.) 21, 115-125]. Purified topoisomerase I from Drosophila embryos, however, is not sufficient for chromatin assembly. Rather, the ability of Drosophila embryo extracts to mediate chromatin assembly in vitro requires an anionic fraction which we demonstrate to be RNA. Exogenous natural and homopolymer RNAs, if of sufficient length, can also mediate chromatin assembly in vitro. The RNA acts stoichiometrically in assembly, being required in amounts at least equal in weight to the amount of histones present. Natural and homopolymer DNAs, whether single or double stranded, are inactive under the same conditions. The arginine-rich histones H3 and H4 or histone H4 alone is sufficient to produce nucleoprotein complexes with physiological numbers of supertwists in the DNA. Complexes containing these subsets of the core histones also resemble assembled complexes containing all four core histones with respect to some patterns of nuclease sensitivity, although complexes containing all four core histones more closely resemble native chromatin in nuclease digestions.


[Study on mechanical performance of the cerebral aneurysm clip].
Blood vessel tissue mechanical performance and cerebral aneurysm clip mechanical property are investigated. Results show that physical character of cerebral aneurysm clip, such as pressure value, maximum opening width of the blade tip, width, thickness and material is very important for its medical purpose. Surveying instrument is devised successfully.


Studies on the mechanism controlling generation of superoxide radical in luteinized rat ovaries during regression.
The mechanism regulating the luteolytic release of superoxide radical (SOR) was examined in prostaglandin F2 alpha (PGF2 alpha)-treated rats. Tail vein injection of PGF2 alpha caused a rapid increase in SOR in mitochondria and plasma membrane samples prepared from luteinized rat ovaries. The peak in the mitochondria preceded that in the plasma membrane, and both occurred before progesterone concentrations decreased in the blood. The amount of SOR produced was greater when samples from the plasma membrane, mitochondria, and cytosol were combined. In plasma membrane samples, SOR generation was lowered by inhibitors of intracellular signaling pathways, but not by cyanide, which blocks electron transport in respiratory enzymes. In mitochondria samples, however, SOR was blocked by cyanide, but not by inhibitors of intracellular signaling enzymes. The addition of phospholipase-A2, phorbol myristate acetate (protein kinase-C activator), or arachidonic acid stimulated SOR production in plasma membrane samples from ovaries of control rats, and phorbol myristate acetate and arachidonic acid inhibited LH-stimulated progesterone secretion in dispersed rat luteal cells. Also, when mitochondria prepared from ovaries of PGF2 alpha-treated rats were added to dispersed corpus luteum cells, there was an increase in SOR generation and an inhibition of LH-stimulated cAMP formation and progesterone secretion. These results indicate that SOR production in the corpus luteum after PGF2 alpha treatment is generated by several subcellular components. Formation in the plasma membrane may be initiated by SOR generation from the mitochondria and regulated by intracellular signaling pathways. Our results indicate that formation of SOR may lead to the disruption of LH stimulation of progesterone secretion.


Mode of action of glyphosate in Candida maltosa.
The broad-spectrum herbicide glyphosate inhibits the growth of Candida maltosa and causes the accumulation of shikimic acid and shikimate-3-phosphate. Glyphosate is a potent inhibitor of three enzymes of aromatic amino acid biosynthesis in this yeast. In relation to tyrosine-sensitive 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase and dehydroquinate synthase, the inhibitory effect appears at concentrations in the mM range, but 5-enolpyruvylshikimate 3-phosphate (EPSP) synthase is inhibited by micromolar concentrations of glyphosate. Inhibition of partially purified EPSP synthase reaction by glyphosate is competitive with respect to phosphoenolpyruvate (PEP) with a Ki-value of 12 microM. The app. Km for PEP is about 5-fold higher and was 62 microM. Furthermore, the presence of glyphosate leads to derepression of many amino acid biosynthetic enzymes.