Pituitary grafts modify sex differences in liver tumor formation in the rat following initiation with diethylnitrosamine and different promotion regimens.
We previously reported on sex differences in chemical hepatocarcinogenesis studied in the resistant hepatocyte model and on the effects of implantation of ectopic pituitary grafts into male rats on the early stages of liver carcinogenesis. Marked sex differences were found in the area ratio of enzyme-altered foci (mm2 foci/cm2 liver section) in sexually mature male and female Wistar rats (male greater than female). Pituitary grafts implanted one week before 2-acetylaminofluorene selection in male rats decreased the area ratio to a level near that of sham operated females. The present study was performed in order to investigate the relevance of the results in the short-term experiment in terms of hepatoma formation. To study the importance of 2-acetylaminofluorene selection as a determinant of the observed sex differences an experiment was also performed using the Pitot-model, where male and female rats were initiated with diethylnitrosamine and promotion was performed with phenobarbital. The long-term experiments in the resistant hepatocyte model showed that male rats develop hepatomas earlier than female rats and also showed a tendency towards a prolonged latency time in male rats bearing pituitary grafts. A good correspondence was thus achieved between the short-term and the long-term experiments. The rats treated according to the Pitot-model did not develop hepatomas within the experimental period. Of the rats killed at 13 months, three (out of five) male and five (out of five) female rats had hepatocyte nodules whereas, at 19 months two (out of six) male and five (out of six) female rats had developed such lesions in this model. We therefore conclude that 2-acetylaminofluorene is the factor responsible for the sex differences in the resistant hepatocyte model and that the hypothalamo-pituitary influence during 2-acetylaminofluorene selection is an important modifier of the carcinogenetic process.


Recombinant adeno-associated virus vectors efficiently and persistently transduce chondrocytes in normal and osteoarthritic human articular cartilage.
Successful gene transfer into articular cartilage is a prerequisite for gene therapy of articular joint disorders. In the present study we tested the hypothesis that recombinant adeno-associated virus (rAAV) vectors are capable of effecting gene transfer in isolated articular chondrocytes in vitro, articular cartilage tissue in vitro, and sites of articular damage in vivo. Using an rAAV vector carrying the Escherichia coli beta-galactosidase gene (lacZ) under the control of the cytomegalovirus (CMV) immediate-early promoter/enhancer (rAAV-lacZ), transduction efficiency exceeded 70% for isolated normal human adult articular chondrocytes, and osteoarthritic human articular chondrocytes. These were comparable to the transduction efficiency obtained with neonatal bovine articular chondrocytes. Transduction of explant cultures of articular cartilage resulted in reporter gene expression within the tissue of all three cartilage types to a depth exceeding 450 microm, which remained present until 150 days. When rAAV-lacZ vectors were applied to femoral chondral defects and osteochondral defects in vivo in a rat knee model, reporter gene expression was achieved for at least 10 days after transduction. These data suggest that AAV-based vectors can efficiently transduce and stably express foreign genes in articular chondrocytes, including chondrocytes of normal and osteoarthritic human articular cartilage. The data further suggest that the same rAAV vectors are capable of transducing chondrocytes in situ within their native matrix to a depth sufficient to be of potential clinical significance. Finally, the data demonstrate that these rAAV vectors are capable of effectively delivering recombinant genes to chondral and osteochondral defects in vivo.


Major satellite repeat RNA stabilize heterochromatin retention of Suv39h enzymes by RNA-nucleosome association and RNA:DNA hybrid formation.
The Suv39h1 and Suv39h2 histone lysine methyltransferases are hallmark enzymes at mammalian heterochromatin. We show here that the mouse Suv39h2 enzyme differs from Suv39h1 by containing an N-terminal basic domain that facilitates retention at mitotic chromatin and provides an additional affinity for major satellite repeat RNA. To analyze an RNA-dependent interaction with chromatin, we purified native nucleosomes from mouse ES cells and detect that Suv39h1 and Suv39h2 exclusively associate with poly-nucleosomes. This association was attenuated upon RNaseH incubation and entirely lost upon RNaseA digestion of native chromatin. Major satellite repeat transcripts remain chromatin-associated and have a secondary structure that favors RNA:DNA hybrid formation. Together, these data reveal an RNA-mediated mechanism for the stable chromatin interaction of the Suv39h KMT and suggest a function for major satellite non-coding RNA in the organization of an RNA-nucleosome scaffold as the underlying structure of mouse heterochromatin.


Cholesterol levels and eicosanoid production in rats fed phosphatidylinositol or soybean lecithin.
Male young rats were fed 8% corn oil diets supplemented either with 2% phosphatidylinositol (PI) from safflower seeds or soybean lecithin (SL) for 22 days. Other groups of rats were fed 10% corn oil diets with or without (control) 0.3% inositol (IN, equivalent to the inositol moiety of the PI diet). The plasma cholesterol level was low in the SL group whereas liver triglyceride was low in all supplemented groups. The aortic production of prostacyclin tended to be high in rats fed the control diet and low in rats fed the SL diet, the PI and IN groups being intermediate. The concentration of plasma thromboxane B2 was comparable among various groups. In plasma and liver phosphatidylcholine, the ratio of arachidonate/linoleate was low in rats fed SL and high in rats fed PI or IN diets. The results indicate that, in addition to SL, the inositol moiety of PI may have a significant role in the regulation of lipid metabolism.


A Tri-Stimuli Responsive (Maghemite/PLGA)/Chitosan Nanostructure with Promising Applications in Lung Cancer.
A (core/shell)/shell nanostructure (production performance ≈ 50%, mean diameter ≈ 330 nm) was built using maghemite, PLGA, and chitosan. An extensive characterization proved the complete inclusion of the maghemite nuclei into the PLGA matrix (by nanoprecipitation solvent evaporation) and the disposition of the chitosan shell onto the nanocomposite (by coacervation). Short-term stability and the adequate magnetism of the nanocomposites were demonstrated by size and electrokinetic determinations, and by defining the first magnetization curve and the responsiveness of the colloid to a permanent magnet, respectively. Safety of the nanoparticles was postulated when considering the results from blood compatibility studies, and toxicity assays against human colonic CCD-18 fibroblasts and colon carcinoma T-84 cells. Cisplatin incorporation to the PLGA matrix generated appropriate loading values (≈15%), and a dual pH- and heat (hyperthermia)-responsive drug release behaviour (≈4.7-fold faster release at pH 5.0 and 45 °C compared to pH 7.4 and 37 °C). The half maximal inhibitory concentration of the cisplatin-loaded nanoparticles against human lung adenocarcinoma A-549 cells was ≈1.6-fold less than that of the free chemotherapeutic. Such a biocompatible and tri-stimuli responsive (maghemite/PLGA)/chitosan nanostructure may found a promising use for the effective treatment of lung cancer.


[Chronic diarrhea: etiologies and diagnostic evaluation].
Chronic diarrhea is defined as a decrease in fecal consistency lasting for four or more weeks. A myriad of disorders are associated with chronic diarrhea. In developed countries, chronic diarrhea is mostly caused by non-infectious diseases. There are four pathogenic mechanisms leading to chronic diarrhea: osmotic diarrhea, secretory diarrhea, inflammatory diarrhea, and dysmotility. Overlaps between these mechanisms are possible. A 72-hour fecal collection as well as the fasting test are important diagnostic tools to identify the underlying pathomechanism. The identification of the pathomechanism narrows down the possible etiologies of chronic diarrhea and allows therefore a cost-saving diagnostic workup. The endoscopy is well established in the workup of chronic diarrhea. This article gives an overview about the main causes and mechanisms leading to chronic diarrhea and proposes an algorithm for the diagnostic evalution.


Sperm donors describe the experience of contact with their donor-conceived offspring.
This study explores the attitudes and experiences of 57 sperm donors who responded to a survey posted online in the United States and indicated that they had had contact with their donor-conceived offspring or the parents of their donor-conceived offspring. On average, 18 years had elapsed since the respondents donated sperm. In the interim between donating and having contact with offspring, most had become curious about their offspring. Most made contact through a bank or online registry. Most respondents had communicated with at least one offspring at least once and most had exchanged photos with offspring. Approximately two-thirds had met in person once; the same proportion had communicated over email or text. Other forms of communication were less common. Almost half of the respondents now considered their donor-conceived offspring to be like a family member. At the same time, donors are respectful of the integrity of the family in which their offspring were raised. Donors with contact are open to having their partners and children know their donor-conceived offspring. Although contact is generally positive, donors report that establishing boundaries and defining the relationship can be very difficult. Some donors also urge those who are thinking of donating to consider the consequences and some suggest avoiding anonymity. There were no significant differences in attitudes and experiences between those who donated anonymously and those who had been identity-release for their offspring when they turned 18.


Method for maximising measurements of muscular pulmonary arteries.
Using a digitiser for assessing the media and intima of muscular pulmonary arteries, we have previously shown that the most sensible measurements are those of medial and intimal area and that artery size should be defined in terms of the total length of internal elastic lamina. These measurements do not vary with the collapse or constriction of the artery. A cross sectional cut and a well defined internal elastic lamina are essential for measurement using our technique. This study explores methods for obtaining the above three measurements for cross sectionally cut arteries with an ill defined internal elastic lamina, with a view to increasing the number of arteries measured. The methods were tested on three subjects, using arteries for which the true values of the three variables were known. Acceptable estimates of medial and intimal area could be obtained by simply delineating the boundaries of the intima and media and ignoring the crinkles in the elastic laminae. It was also found that muscular pulmonary arteries may not be uniformly collapsed or constricted round the circumference of their walls and that the overall degree of collapse or constriction seemed to be affected by the size of the artery. An acceptable estimate of the total length of an internal elastic lamina was most readily obtained by multiplying the length of the boundary between intima and media by a crinkle factor based on an optical assessment of the amount of crinkling in that internal elastic lamina.


Automated medical records technology at the National Cancer Institute-Egypt: a case study in technology transfer.
The National Cancer Institute-Cairo, Egypt (NCI) has adopted three different approaches to the automated medical record. These approaches are: the use of an integrated hospital information system, a document scanning system, and an imaging system. This paper discusses each of these approaches with regard to its benefits, technology-implemented and technology-related issues, and the social and cultural differences between implementations in developed and developing countries.


Noradrenergic function and the mechanism of action of antianxiety treatment. I. The effect of long-term alprazolam treatment.
There is preclinical and clinical evidence suggesting that one neural mechanism responsible for antipanic efficacy is a reduction in brain noradrenergic function. Alprazolam, a triazolobenzodiazepine, has been demonstrated to have antipanic properties; however, to our knowledge, its effects on noradrenergic function have not been established. To assess whether alprazolam alters noradrenergic function, the effects of alprazolam on baseline plasma free 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), and yohimbine-induced increases in plasma MHPG level, anxiety-nervousness, blood pressure, and somatic symptoms were studied in 14 patients with agoraphobia and panic disorder. Long-term alprazolam treatment significantly reduced plasma MHPG baseline and blunted the yohimbine-induced increases in plasma MHPG, anxiety-nervousness, and sitting systolic blood pressure. These observations suggest that the antipanic mechanism of action of alprazolam may be due in part to an interaction between benzodiazepine-sensitive and noradrenergic neural systems.


Translational control of the antiapoptotic function of Ras.
Activated Ras has been shown to provide powerful antiapoptotic signals to cells through well defined transcriptional and post- translational pathways, whereas translational control as a mechanism of Ras survival signaling remains unexplored. Here we show a direct relationship between assembly of the cap-dependent translation initiation apparatus and suppression of apoptosis by oncogenic Ras in vitro and in vivo. Decreasing protein synthesis with rapamycin, which is known to inhibit cap-dependent translation, increases the susceptibility of Ras-transformed fibroblasts to cytostatic drug-induced apoptosis. In contrast, suppressing global protein synthesis with equipotent concentrations of cycloheximide actually prevents apoptosis. Enforced expression of the cap-dependent translational repressor, the eukaryotic translation initiation factor (eIF) 4E-binding protein (4E-BPI), sensitizes fibroblasts to apoptosis in a manner strictly dependent on its ability to sequester eIF4E from a translationally active complex with eIF4GI and the co-expression of oncogenic Ras. Ectopic expression of 4E-BP1 also promotes apoptosis of Ras-transformed cells injected into immunodeficient mice and markedly diminishes their tumorigenicity. These results establish that eIF4E-dependent protein synthesis is essential for survival of fibroblasts bearing oncogenic Ras and support the concept that activation of cap-dependent translation by extracellular ligands or intrinsic survival signaling molecules suppresses apoptosis, whereas synthesis of proteins mediating apoptosis can occur independently of the cap.


A miniaturized solid salt reverse electrodialysis battery: a durable and fully ionic power source.
A novel pump-free miniaturized reverse electrodialysis (RED) system was designed to provide lasting power transduced from salinity gradients, named solid salt RED (ssRED), and this quasi-battery uses a solid salt instead of electrolyte solution for streamlined usage. It is portable, flexible, comparable in size to a universal serial bus flash drive, and easily activated with a small amount of water. It maintains a constant ionic concentration gradient through precipitation reactions between a pair of different salts. This precipitation-assisted solid salt RED (PssRED) is an unprecedented ionic power source as it can generate steady electricity in the absence of a driving pump. The PssRED was successfully coupled with bipolar electrode (BPE) microchip sensors which require stable ionic electricity and a polyelectrolyte ionic diode to realize a fully ionic circuit. It is envisioned that the range of application could be expanded to supply electromotive force to various devices through an ionic charge flow.


In utero repair of experimental myelomeningocele saves neurological function at birth.
In a previous series of fetal sheep experiments, the authors demonstrated that midgestational exposure of the normal spinal cord to the amniotic space leads to a myelomeningocele (MMC) at birth that closely resembles human MMC phenotypes in terms of morphology and functional deficit. The present study tested whether delayed in utero repair of such evolving experimental MMC lesions spares neurological function. In 12 sheep fetuses, a spina bifida-type lesion with exposure of the lumbar spinal cord was created at 75 days' gestation (full term, 150 days). Four weeks later, the developing MMC lesions were repaired in utero for seven fetuses (five fetuses died before this time). Of those that had repair, three were delivered near term by cesarean section, and four died in utero or were aborted. All survivors had healed skin wounds and near-normal neurological function. Despite mild paraparesis, they were able to stand, walk, and perform demanding motor tests. Sensory function of the hindlimbs was present clinically and confirmed electrophysiologically. No signs of incontinence were detected. Histologically, the exposed and then covered spinal cord showed significant deformation, but the anatomic hallmarks as well as the cytoarchitecture of the spinal cord essentially were preserved. These findings show that timely in utero repair of developing experimental MMC stops the otherwise ongoing process of spinal cord destruction and "rescues" neurological function by the time of birth. Because there is evidence that a similar secondary damage to the exposed neural tissue also occurs in human MMC, we propose that in utero repair of selected human fetuses might reduce the neurological disaster commonly encountered after birth.


Towards the treatment of polyglutamine diseases: the modulatory role of protein context.
Protein aggregation is a key mechanism involved in neurodegeneration associated with Alzheimer's, Parkinson's and Huntington's diseases. Nine diseases (including Huntington's) arise from polyglutamine (polyQ) expansion above a repeat threshold of approximately 37 glutamines, and neuronal toxicity correlates with the process of protein aggregation. The similar toxic gain-of-function mechanism of the nine diseases supports the hypothesis that disease onset and progression is dependent upon polyQ expansion. However, there is an increasing body of literature demonstrating that the protein context of the polyQ tract has an essential role in the disease process. The composition of regions flanking repeats can alter the biochemical and biophysical properties of the polyQ region. A number of the disease proteins are proteolytically cleaved, with release of the polyQ-containing fragment initiating aggregation. Interactions of flanking domains with other molecules can also influence aggregation and cellular localization, which are critical factors for toxicity. More recently, there is evidence that domains flanking the polyQ tract can also aggregate independent of the polyQ tract, and that this significantly alters the rate at which the polyQ regions form fibrillar aggregates and the properties of these aggregates. In this review we consider the role of protein context in modulating the polyQ diseases and the therapeutic potential of targeting non-polyQ protein properties.


Development and Validation of a Postprocedural Model to Predict Outcome After Endovascular Treatment for Ischemic Stroke.
Outcome prediction after endovascular treatment (EVT) for ischemic stroke is important to patients, family members, and physicians. To develop and validate a model based on preprocedural and postprocedural characteristics to predict functional outcome for individual patients after EVT. A prediction model was developed using individual patient data from 7 randomized clinical trials, performed between December 2010 and December 2014. The model was developed within the Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials (HERMES) collaboration and external validation in data from the Dutch Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry of patients treated in clinical practice between March 2014 and November 2017. Participants included patients from multiple centers throughout different countries in Europe, North America, East Asia, and Oceania (derivation cohort), and multiple centers in the Netherlands (validation cohort). Included were adult patients with a history of ischemic stroke from an intracranial large vessel occlusion in the anterior circulation who underwent EVT within 12 hours of symptom onset or last seen well. Data were last analyzed in July 2022. A total of 19 variables were assessed by multivariable ordinal regression to predict functional outcome (modified Rankin Scale [mRS] score) 90 days after EVT. Variables were routinely available 1 day after EVT. Akaike information criterion (AIC) was used to optimize model fit vs model complexity. Probabilities for functional independence (mRS 0-2) and survival (mRS 0-5) were derived from the ordinal model. Model performance was expressed with discrimination (C statistic) and calibration. A total of 781 patients (median [IQR] age, 67 [57-76] years; 414 men [53%]) constituted the derivation cohort, and 3260 patients (median [IQR] age, 72 [61-80] years; 1684 men [52%]) composed the validation cohort. Nine variables were included in the model: age, baseline National Institutes of Health Stroke Scale (NIHSS) score, prestroke mRS score, history of diabetes, occlusion location, collateral score, reperfusion grade, NIHSS score at 24 hours, and symptomatic intracranial hemorrhage 24 hours after EVT. External validation in the MR CLEAN Registry showed excellent discriminative ability for functional independence (C statistic, 0.91; 95% CI, 0.90-0.92) and survival (0.89; 95% CI, 0.88-0.90). The proportion of functional independence in the MR CLEAN Registry was systematically higher than predicted by the model (41% vs 34%), whereas observed and predicted survival were similar (72% vs 75%). The model was updated and implemented for clinical use. The prognostic tool MR PREDICTS@24H can be applied 1 day after EVT to accurately predict functional outcome for individual patients at 90 days and to provide reliable outcome expectations and personalize follow-up and rehabilitation plans. It will need further validation and updating for contemporary patients.


Location-Specific Association Between Cerebral Microbleeds and Arterial Pulsatility.
Objective: Increased arterial pulsatility index (API), usually representative of distal vascular resistance, have been linked to cerebral small vessel disease. However, their relationship with cerebral microbleeds (CMBs) is less well-studied. The present study aimed to evaluate the relationship between CMBs and API. Methods: We cross-sectionally evaluated participants from a non-clinical stroke, non-demented community-based population. APIs of cervical internal carotid and vertebral arteries were measured by ultrasonography. CMBs were assessed by susceptibility-weighted-imaging on 3T magnetic resonance imaging (MRI). Subjects were classified according to CMB locations: deep/infratentorial (DI) or strictly lobar (SL) CMB groups. DI-CMB group also included subjects with simultaneous lobar CMBs. Results: Of the 681 subjects [62.2 (8.4) years, 43.5% men] included, CMBs were found in 92 (13.5%) subjects: 57 (8.4%) with DI-CMB and 35 (5.1%) with SL-CMB. The results showed that CMB location influenced their association with API. DI-CMB was significantly associated with elevated API of internal carotid arteries (β = 0.031; 95% confidence interval = 0.002-0.059; P = 0.03), while SL-CMB was significantly associated with elevated API of vertebral arteries (β = 0.050; 95% confidence interval = 0.006-0.094; P = 0.025) in multivariate analyses adjusting for age, sex, cardiovascular risk factors, white matter hyperintensities (WMH), and lacunes. Conclusion: Our study again emphasizes (1) the association between API and cerebral small vessel disease and (2) the pathogenic differences between DI- and SL-CMBs. Our results lead to the postulation that in the presence of CMBs without clinical dysfunction yet, insidious small vascular disorders might already occur with corresponding topography.


New Methyl Methacrylate Derived Adsorbents - Synthesis, Characterization and Adsorptive Removal of Toxic Organic Compounds.
This study aimed to synthesize polymeric adsorbents by suspension polymerization using methyl methacrylate (MMA) with different crosslinking monomers. Divinylbenzene (DVB) and aliphatic monomers: ethylene glycol dimethacrylate (EGDMA) or N,N'-methylenebisacrylamide (NN) containing additional amide groups were used. The possibility of using the prepared copolymers (MMA-NN, MMA-EGDMA, MMA-DVB) as adsorbents for the removal of toxic compounds such as dyes (C.I. Acid Red 18 (AR18), C.I. Acid Green 16 (AG16), C.I. Acid Violet 1 (AV1), C.I. Basic Yellow 2 (BY2), C.I. Basic Blue 3 (BB3) and C.I. Basic Red 46 (BR46)) and phenol (PhOH) from dye baths and effluents was evaluated. Preferential adsorption of basic-type dyes compared to acid-type dyes or phenol was observed by the polymers. Adsorbent based on MMA-EGDMA exhibited the highest capacity for investigated dyes and phenol. The pseudo-second order kinetic model as well as the intraparticle diffusion model can find application in predicting sorption kinetics. Based on the equilibrium sorption data fitted to the Langmuir, Freundlich, Temkin and Dubinin-Radushkevich model, uptake of BB3, AV1 and PhOH is rather physisorption than chemisorption. The regeneration yield of MMA-EGDMA does not exceed 60 % using 1 M HCl, 1 M NaCl, and 1 M NaOH in 50 %v/v methanol.


Exploratory comparison of flower visiting behavior and pollination ability of mason bees, bumble bees, and honey bees.
This study explored the flower visiting behaviors and pollination abilities of mason bees (Osmia excavata Alfken (Hymenoptera: Megachilidae)), bumble bees (Bombus terrestris (Linnaeus, 1758) (Hymenoptera: Apidae)), and Italian honey bees (Apis mellifera ligustica Spinola (Hymenoptera: Apidae)) in apple orchards in early spring in Jinan (located in the central region of Shandong) and Yantai (located in the Peninsula of Shandong). We compared the pollen collection patterns, flower visiting behavior, flying speed, and effects on apple pollination of the 3 types of bees. The frequencies of flower visits were significantly higher for mason bees (12.89/min in Jinan and 10.63/min in Yantai) than bumble bees and Italian honey bees in the 2 regions. The single flower residence times were significantly higher for Italian honey bees (8.22 s in Jinan and 9.43 s in Yantai), but Italian honey bees were most affected by the climate. The 3 bees differed significantly in terms of the amount of apple pollen collected and their effects on the fruit setting rate in apples (mason bees > bumble bees > Italian honey bees). The results showed that the mason bee was the most suitable pollinating species for spring apple orchards; Bumble bees were more suitable as alternative pollinators during cloudy and low temperatures; Italian honey bees were able to take advantage of their large number of worker bees in sunny and warm weather. Compared to individual bee species, a combination of 2 or 3 species of bees might be more advantageous in dealing with complex and variable weather conditions.


High-Yield Production of Chimeric Hepatitis E Virus-Like Particles Bearing the M2e Influenza Epitope and Receptor Binding Domain of SARS-CoV-2 in Plants Using Viral Vectors.
Capsid protein of Hepatitis E virus (HEV) is capable of self-assembly into virus-like particles (VLPs) when expressed in Nicotiana benthamiana plants. Such VLPs could be used as carriers of antigens for vaccine development. In this study, we obtained VLPs based on truncated coat protein of HEV bearing the M2e peptide of Influenza A virus or receptor-binding domain of SARS-CoV-2 spike glycoprotein (RBD). We optimized the immunogenic epitopes' presentation by inserting them into the protruding domain of HEV ORF2 at position Tyr485. The fusion proteins were expressed in Nicotiana benthamiana plants using self-replicating potato virus X (PVX)-based vector. The fusion protein HEV/M2, targeted to the cytosol, was expressed at the level of about 300-400 μg per gram of fresh leaf tissue and appeared to be soluble. The fusion protein was purified using metal affinity chromatography under native conditions with the final yield about 200 μg per gram of fresh leaf tissue. The fusion protein HEV/RBD, targeted to the endoplasmic reticulum, was expressed at about 80-100 μg per gram of fresh leaf tissue; the yield after purification was up to 20 μg per gram of fresh leaf tissue. The recombinant proteins HEV/M2 and HEV/RBD formed nanosized virus-like particles that could be recognized by antibodies against inserted epitopes. The ELISA assay showed that antibodies of COVID-19 patients can bind plant-produced HEV/RBD virus-like particles. This study shows that HEV capsid protein is a promising carrier for presentation of foreign antigen.


Efficient conversion of biomass into lipids by using the simultaneous saccharification and enhanced lipid production process.
Microbial lipid production by using lignocellulosic biomass as the feedstock holds a great promise for biodiesel production and biorefinery. This usually involves hydrolysis of biomass into sugar-rich hydrolysates, which are then used by oleaginous microorganisms as the carbon and energy sources to produce lipids. However, the costs of microbial lipids remain prohibitively high for commercialization. More efficient and integrated processes are pivotal for better techno-economics of microbial lipid technology. Here we describe the simultaneous saccharification and enhanced lipid production (SSELP) process that is highly advantageous in terms of converting cellulosic materials into lipids, as it integrates cellulose biomass hydrolysis and lipid biosynthesis. Specifically, Cryptococcus curvatus cells prepared in a nutrient-rich medium were inoculated at high dosage for lipid production in biomass suspension in the presence of hydrolytic enzymes without auxiliary nutrients. When cellulose was loaded at 32.3 g/L, cellulose conversion, cell mass, lipid content and lipid coefficient reached 98.5%, 12.4 g/L, 59.9% and 204 mg/g, respectively. Lipid yields of the SSELP process were higher than those obtained by using the conventional process where cellulose was hydrolyzed separately. When ionic liquid pretreated corn stover was used, both cellulose and hemicellulose were consumed simultaneously. No xylose was accumulated over time, indicating that glucose effect was circumvented. The lipid yield reached 112 mg/g regenerated corn stover. This process could be performed without sterilization because of the absence of auxiliary nutrients for bacterial contamination. The SSELP process facilitates direct conversion of both cellulose and hemicellulose of lignocellulosic materials into microbial lipids. It greatly reduces time and capital costs while improves lipid coefficient. Optimization of the SSELP process at different levels should further improve the efficiency of microbial lipid technology, which in turn, promote the biotechnological production of fatty acid-derived products from lignocellulosic biomass.


[Some properties of bacteriocins from Erwinia].
The following properties of eight bacteriocins produced by Erwinia strains were investigated: thermal stability, sensitivity to proteolytc enzymes and enzymes involved in nucleic acid catabolism, dialyzability through a cellophane membrane. Their molecular weight was also measured. The bacteriocins proved to be protein substances with a molecular weight of 17,000--33,000 that differed in their thermal stability and sensitivity to proteolytic enzymes.


Relabeling algorithm for retrieval of noisy instances and improving prediction quality.
A relabeling algorithm for retrieval of noisy instances with binary outcomes is presented. The relabeling algorithm iteratively retrieves, selects, and re-labels data instances (i.e., transforms a decision space) to improve prediction quality. It emphasizes knowledge generalization and confidence rather than classification accuracy. A confidence index incorporating classification accuracy, prediction error, impurities in the relabeled dataset, and cluster purities was designed. The proposed approach is illustrated with a binary outcome dataset and was successfully tested on the standard benchmark four UCI repository dataset as well as bladder cancer immunotherapy data. A subset of the most stable instances (i.e., 7% to 51% of the sample) with high confidence (i.e., between 64%-99.44%) was identified for each application along with most noisy instances. The domain experts and the extracted knowledge validated the relabeled instances and corresponding confidence indexes. The relabeling algorithm with some modifications can be applied to other medical, industrial, and service domains.


Identification of ecotropic proviral sequences in high- and low-ecotropic-virus-producing mouse strains.
The arrangement of endogenous ecotropic retroviruses in selected high- and low-ecotropic-virus-producing mouse strains was examined by Southern blot hybridization analysis, using an ecotropic retrovirus-specific DNA probe. High-ecotropic-virus-producing mouse strains of the AKR family displayed heterogeneity with respect to the number of copies and the sites of insertion of endogenous ecotropic specific DNA. This diversity was seen even among individuals of the same AKR subline. Contrastingly, individuals within the same low-ecotropic-retrovirus-producing mouse strain showed no evidence of variability in their endogenous ecotropic proviral sequences. These results favored the hypothesis that germ line proviral reinsertion was responsible for the proviral sequence heterogeneity observed in high-ecotropic-virus-producing mouse strains.


AMP-activated protein kinase agonist dose dependently improves function and reduces apoptosis in glucotoxic beta-cells without changing triglyceride levels.
Prolonged hyperglycaemia leads to impaired glucose-stimulated insulin secretion (GSIS) and apoptosis in insulin-producing beta-cells. The detrimental effects have been connected with glucose-induced lipid accumulation in the beta-cell. AMP-activated protein kinase (AMPK) agonist, 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), promotes utilization of nutrient stores for energy production. It was tested how impaired GSIS and elevated apoptosis observed in insulinoma (INS)-1E cells after prolonged culture at 27 mM glucose were affected by the inclusion of 0.3 or 1 mM AICAR during culture. Glucose-induced impairment of insulin release was reverted by the inclusion of 0.3 but not 1 mM AICAR, which did not affect insulin content. The glucose-induced rise in triglyceride (TG) content observed in the cells cultured at 27 mM glucose was not altered by the inclusion of either 0.3 or 1 mM AICAR. Inclusion of 1 but not 0.3 mM AICAR during culture induced phosphorylation of AMPK and its downstream target acyl-CoA carboxylase. Phosphorylation was paralleled by reduced number of apoptotic cells and lowered expression of pro-apoptotic C/EBP homologous protein (CHOP). In conclusion, AICAR dose dependently improves beta-cell function and reduces apoptosis in beta-cells exposed to prolonged hyperglycaemia without changing TG levels.


The resting brain and our self: self-relatedness modulates resting state neural activity in cortical midline structures.
The resting brain shows high neural activity in various regions, the default-mode network, chief among them the cortical midline structures (CMS). The psychological correlate of high resting state neural activity in CMS remains however unclear though speculatively it has been associated with processing of internally-oriented self-relatedness. We used functional MRI to examine internally-oriented self-relatedness during the resting state period. This was indirectly done by letting subjects perceive emotional pictures followed by a fixation cross; the very same pictures were then rated subjectively according to their degree of self-relatedness in a postscanning session. This allowed us to correlate the picture ratings of self-relatedness with signal changes in the subsequent resting state period, i.e. fixation period. The emotional pictures' degree of self-relatedness parametrically modulated subsequent resting state signal changes in various CMS, including ventro- and dorsomedial prefrontal cortex and posterior cingulate cortex. This modulation could be distinguished from effects of emotion dimensions (e.g. valence, intensity) and evoked effects of self-relatedness during the stimulus period itself the latter being observed rather in subcortical regions, e.g. amygdala, ventral striatum, and tectum. In sum, our findings suggest that resting state neural activity in CMS is parametrically and specifically modulated by the preceding stimulus's degree of self-relatedness. This lends further support to the presumed involvement of these regions in processing internally-oriented self-relatedness as distinguished from externally-oriented self-relatedness.


Examining the Effects of Postmastectomy Radiation Therapy in Prepectoral Versus Subpectoral Autologous Breast Reconstruction.
Postmastectomy radiation therapy (PMRT) is known to increase the risk of multiple adverse outcomes after breast reconstruction. In the context of delayed-immediate autologous breast reconstruction, PMRT is typically conducted after placement of subpectoral (SP) tissue expanders. With the re-emergence of prepectoral (PP) reconstruction, there are little data assessing the outcomes of PP reconstruction in breasts receiving PMRT. We compared postoperative outcomes of PMRT patients undergoing delayed-immediate, autologous breast reconstruction with placement of tissue expanders in either the PP or SP plane. A retrospective chart review was conducted on all consecutive patients who underwent delayed-immediate autologous breast reconstruction and received PMRT at either the Stanford University or the Johns Hopkins University Hospitals between January 2009 and December 2018. Demographics, comorbidities, perioperative information, and oncologic data were collected for all patients. Complications were collected and analyzed after stage 1 surgery, between 30 days of stage 1 and up to stage 2 surgery, and after stage 2 surgery. Multivariable regressions were used to determine predictors of 1 or more complications. A total of 71 patients (73 breasts) were included. Prepectoral reconstruction comprised of 52.2% of the cohort, and the remaining 47.8% were SP reconstructions. Demographics and comorbidities were similar between groups, except for premastectomy radiation, which was more prevalent in the PP cohort (P = 0.010). Complications were similar between cohorts after stage 1 surgery (P = 0.420), between stages 1 and 2 (P = 0.100), and after stage 2 (P = 0.570). There were higher rates of skin necrosis in the SP cohort between stages 1 and 2 (PP: 2.6%, SP: 20%, P = 0.004). Multivariable analysis revealed body mass index to be the only predictor of complication (P = 0.041). The mean number of revisionary surgeries was higher in the SP cohort (PP: 0.8 vs SP: 1.9, P = 0.002). The mean follow-up was 385.5 days and similar between groups (P = 0.870). Rates of overall complication were similar between PP and SP expander placement. However, in SP reconstructions, skin necrosis was significantly higher between stages 1 and 2. The patients in the SP cohort also underwent a greater number of revisionary surgeries, although overall rates of pursuing any revisionary surgery were similar between groups.


Insights into unique features of Drosophila CYP4G enzymes.
The cytochrome P450 enzymes of the CYP4G subfamily are some of the most intriguing insect P450s in terms of structure and function. In Drosophila, CYP4G1 is highly expressed in the oenocytes and is the last enzyme in the biosynthesis of cuticular hydrocarbons, while CYP4G15 is expressed in the brain and is of unknown function. Both proteins have a CYP4G-specific and characteristic amino acid sequence insertion corresponding to a loop between the G and H helices whose function is unclear. Here we address these enigmatic structural and functional features of Drosophila CYP4Gs. First, we used reverse genetics to generate D. melanogaster strains in which all or part of the CYP4G-specific loop was removed from CYP4G1. We showed that the full loop was not needed for proper folding of the P450, but it is essential for function, and that just a short stretch of six amino acids is required for the enzyme's ability to make hydrocarbons. Second, we confirmed by immunocytochemistry that CYP4G15 is expressed in the brain and showed that it is specifically associated with the cortex glia cell subtype. We then expressed CYP4G15 ectopically in oenocytes, revealing that it can produce of a blend of hydrocarbons, albeit to quantitatively lower levels resulting in only a partial rescue of CYP4G1 knockdown flies. The CYP4G1 structural variants studied here should facilitate the biochemical characterization of CYP4G enzymes. Our results also raise the question of the putative role of hydrocarbons and their synthesis by cortex glial cells.


Prompt laparoscopic cholecystectomy would reduce morbidity and save hospital resources.
Limited resources and organisational problems often result in significant waiting times for patients presenting with an indication for cholecystectomy. This study investigated the potential false economy of such practice. Retrospective analysis of all patients on a waiting list for cholecystectomy between July 2007 and October 2010 was performed. The hospital computer document management system and patients' notes were used to collect data. A total of 1,021 patients were included in the study; 701 were listed from clinic and 320 were listed following an emergency admission. The median time on a waiting list before surgery was 96 days (range: 5-381 days). Eighty-seven patients (8.5%) had an emergency admission with a gallstone related problem while on a waiting list. This resulted in 488 cumulative inpatient days. There was a significant correlation between increased time spent on the waiting list and increased chance of an emergency admission (p=0.01). Patients added to the waiting list from emergency admissions were more likely to be admitted with complications than those listed from clinic (15.3% vs 5.4%, p<0.01). There was no association between age (p=0.53) or sex (p=0.23) and likelihood of emergency admission while on a waiting list. Prompt elective surgery and same-admission emergency laparoscopic cholecystectomy can reduce waiting list patient morbidity and is likely to save resources in the long term.


Investigating the prevalence of queuine in Escherichia coli RNA via incorporation of the tritium-labeled precursor, preQ(1).
There are over 100 modified bases that occur in RNA with the majority found in transfer RNA. It has been widely believed that the queuine modification is limited to four transfer RNA species in vivo. However, given the vast amount of the human genome (60-70%) that is transcribed into non-coding RNA (Mattick [10]), probing the presence of modified bases in these RNAs is of fundamental importance. The mechanism of incorporation of queuine, via transglycosylation, makes this uniquely poised to probe base modification in RNA. Results of incubations of Escherichia coli cell cultures with [(3)H] preQ(1) (a queuine precursor in eubacteria) clearly demonstrate preQ(1) incorporation into a number of RNA species of various sizes larger than transfer RNA. Specifically, significant levels of preQ(1) incorporation into ribosomal RNA are observed. The modification of other large RNAs was also observed. These results confirm that non-coding RNAs contain modified bases and lead to the supposition that these modifications are necessary to control non-coding RNA structure and function as has been shown for transfer RNA.


[Basic principles of immunocorrection in otorhinolaryngology].
Immunocorrection in otorhinolaryngology is primarily local. Stimulating immunomodulators are most widely employed. Introduction of immunocorrection in combined treatment of secondary immunodeficiency in ENT diseases entails conduction of a wide range of immunological tests. Immunocorrectors should be selected strictly on the individual basis.


Root-Associated Microbiomes, Growth and Health of Ornamental Geophytes Treated with Commercial Plant Growth-Promoting Products.
The microbial community inhabiting a plant's root zone plays a crucial role in plant health and protection. To assess the ability of commercial plant growth-promoting products to enhance the positive effects of this environment, two products containing beneficial soil bacteria and a product containing plant extracts were tested on Zantedeschia aethiopica and Ornithogalum dubium. The products were tested in two different growing media: a soil and a soilless medium. The effects of these products on Pectobacterium brasiliense, the causal agent of soft rot disease, were also evaluated in vitro, and on naturally occurring infections in the greenhouse. The growing medium was found to have the strongest effect on the microbial diversity of the root-associated microbiome, with the next-strongest effect due to plant type. These results demonstrate that either a single bacterial strain or a product will scarcely reach the level that is required to influence soil microbial communities. In addition, the microbes cultured from these products, could not directly inhibit Pectobacterium growth in vitro. We suggest density-based and functional analyses in the future, to study the specific interactions between plants, soil type, soil microbiota and relevant pathogens. This should increase the effectiveness of bio-supplements and soil disinfestation with natural products, leading to more sustainable, environmentally friendly solutions for the control of bacterial plant diseases.


Surgical navigation based on fluoroscopy--clinical application for computer-assisted distal locking of intramedullary implants.
Fluoroscopy is used to guide surgical instruments during orthopedic procedures. Radiation exposure and lack of spatial information are drawbacks of this method. Improvements are expected when fluoroscopy-based surgical navigation is used for intraoperative guidance, e.g., in computer-assisted distal locking of intramedullary implants. The method was applied to 42 interlocking procedures during implantation of the short proximal femoral nail in 27 patients with pertrochanteric femoral fractures. Precision of interlocking, exposure time, operating time, and number of personnel required for computer-assisted distal locking were recorded. One misplaced interlocking screw was observed (2.3%), and contact between the drill bit and the nail during drilling was noticed in 8 cases (19%). The average exposure time was 16 seconds (range 4-42 seconds), and the procedure took an average of 43 min (range 20-70 min). The number of persons required for computer-assisted distal locking was reduced from three to one within the course of the study. Fluoroscopy-based surgical navigation provided precise intraoperative guidance for computer-assisted distal locking with minimal use of fluoroscopy. The complex system and related procedure times may be drawbacks in this application. Clinical studies are underway to define implants and surgical procedures where intraoperative guidance by fluoroscopy-based surgical navigation is beneficial for the patient and/or surgeon.


Comparison of metastasis of mammary tumors growing in the mammary fatpad versus the subcutis.
The frequency with which metastasis occurs for three tumor sublines derived from a single mouse mammary tumor, all of which grow preferentially in mammary fatpads (as compared to the subcutis), was determined from primary tumors growing in mammary fatpads and from primary tumors growing in the subcutis. A relatively metastatic subline was found to metastasize more readily from the mammary fatpad than from subcutaneous sites. The number of metastatic nodules found in the lungs of animals following surgical removal of primary tumors transplanted into intact mammary fatpads was significantly greater than the number of nodules in the lungs of animals following surgical removal of primary tumors transplanted subcutaneously. Two sublines, which do not readily metastasize from tumors growing subcutaneously, did not metastasize from tumors growing in mammary fatpads.


Hypotensive agents from snake venoms.
Many snake venoms contain toxins which produce profound cardiovascular effects. The site of action of these toxins includes cardiac muscle, vascular smooth muscle and the capillary vascular bed. Some snake venoms, for example, contain peptides that inhibit angiotensin converting enzyme and potentiate the biological actions of bradykinin. Other snake venoms contain structural and functional equivalents of mammalian natriuretic peptides. Sarafotoxins are short peptide toxins found in the venoms of snakes from Atractaspis spp. which display potent vasoconstriction properties. These peptides, which share a high degree of sequence identity with endothelins, recognize and bind to endothelin receptors. Snakes have also evolved toxins which block L-type Ca(2+) currents (eg. calciseptine, FS2 toxins, C(10)S(2)C(2) and S(4)C(8)). Snake venom proteins have also been shown to increase vascular permeability. One such protein, increasing capillary permeability protein (ICPP) has recently been isolated from the venom of Vipera lebetina. ICPP is an extremely potent permeability factor with a structure similar to vascular endothelial growth factor (VEGF). Thus there is a vast array of snake toxins with potent cardiovascular activity. Some of these proteins and peptides have proven to be highly selective tools in the study of physiological processes. Others have been used as probes of potential therapeutic targets or as lead compounds in the development of therapeutic agents. Therefore these and other related snake venom proteins hold great promise in the future understanding and treatment of cardiovascular diseases.


Effect of a megadose of ascorbic acid, a meal and orange juice on the absorption of selenium as sodium selenite.
Urinary and faecal excretions of selenium were measured for five days following a dose of 1 mg Se as sodium selenite in ten young women after an overnight fast. The selenite was taken two hours before a meal or mixed with 1 g ascorbic acid; or with a continental type breakfast providing 4.5-5.6 micrograms Se and 0.6-0.8 mg Cu, with or without 200 ml orange juice (60 mg ascorbic acid). The light meal appeared to have little effect on selenite-Se absorption, and orange juice appeared even to assist it. But the availability of Se was reduced almost to zero when selenite and 1 g ascorbic acid were taken together well before the meal.


Isolation and expression of a chicken DNA methyltransferase cDNA.
A 0.5 kb fragment of chicken DNA methyltransferase cDNA was PCR-amplified using a set of degenerate primers. A clone harboring a 5 kb insert was isolated from a cDNA library by screening with the PCR-amplified cDNA fragment as a probe. The elucidated nucleotide sequence gave a 4,614 nucleotide open reading frame, and the predicted protein was highly homologous to the mouse and human DNA methyltransferases, especially in the amino acid sequence of the catalytic domain in the carboxyl-terminal region. The cysteine-rich region and Lys-Gly repeat first found in the mouse sequence were also conserved in chicken. However, about 250 amino acid residues in the amino-terminal portion of chicken DNA methyltransferase diverged from the amino-terminus of the mouse or human sequence. Northern blot analysis showed that the message of chicken DNA methyltransferase was expressed at high levels in the testis, in the lung and in Marek's virus-transformed chicken T-lymphoma cells. Expression of the chicken DNA methyltransferase in COS1 cells demonstrated that the enzyme is a so-called maintenance-type methylase. When poly(dG-dC)-poly(dG-dC) was used as the methyl acceptor, to provide a measure of de novo methylase activity, the Km value for S-adenosyl L-methionine was about 5 microM, which was 10 times higher than that when poly(dI-dC)-poly(dI-dC) was used. The affinity of DNA methyltransferase for S-adenosyl L-methionine in catalyzing de novo-type methylation activity was lower than that in catalyzing maintenance-type activity, though it was still high enough for the enzyme to work as a de novo-type methylase under physiological conditions.


Evaluation of a (64)Cu-labeled cystine-knot peptide based on agouti-related protein for PET of tumors expressing alphavbeta3 integrin.
Recently, a truncated form of the agouti-related protein (AgRP), a 4-kDa cystine-knot peptide of human origin, was used as a scaffold to engineer mutants that bound to alpha(v)beta(3) integrin with high affinity and specificity. In this study, we evaluated the potential of engineered integrin-binding AgRP peptides for use as cancer imaging agents in living subjects. Engineered AgRP peptides were prepared by solid-phase peptide synthesis and were folded in vitro and purified by reversed-phase high-performance liquid chromatography. Competition assays were used to measure the relative binding affinities of engineered AgRP peptides for integrin receptors expressed on the surface of U87MG glioblastoma cells. The highest-affinity mutant, AgRP clone 7C, was site-specifically conjugated with 1,4,7,10-tetra-azacyclododecane-N,N',N''N'''-tetraacetic acid (DOTA). The resulting bioconjugate, DOTA-AgRP-7C, was radiolabeled with (64)Cu for biodistribution analysis and small-animal PET studies in mice bearing U87MG tumor xenografts. In addition to serum stability, the in vivo metabolic stability of (64)Cu-DOTA-AgRP-7C was assessed after injection and probe recovery from mouse kidney, liver, tumor, and urine. AgRP-7C and DOTA-AgRP-7C bound with high affinity to integrin receptors expressed on U87MG cells (half maximal inhibitory concentration values, 20 +/- 4 and 14 +/- 2 nM, respectively). DOTA-AgRP-7C was labeled with (64)Cu with high radiochemical purity (>99%). In biodistribution and small-animal PET studies, (64)Cu-DOTA-AgRP-7C displayed rapid blood clearance, good tumor uptake and retention (2.70 +/- 0.93 percentage injected dose per gram [%ID/g] and 2.37 +/- 1.04 %ID/g at 2 and 24 h, respectively), and high tumor-to-background tissue ratios. The integrin-binding specificity of (64)Cu-DOTA-AgRP-7C was confirmed in vitro and in vivo by showing that a large molar excess of the unlabeled peptidomimetic c(RGDyK) could block probe binding and tumor uptake. Serum stability and in vivo metabolite assays demonstrated that engineered AgRP peptides are sufficiently stable for in vivo molecular imaging applications. A radiolabeled version of the engineered AgRP peptide 7C showed promise as a PET agent for tumors that express the alpha(v)beta(3) integrin. Collectively, these results validate AgRP-based cystine-knot peptides for use in vivo as molecular imaging agents and provide support for the general use of AgRP as a scaffold to develop targeting peptides, and hence diagnostics, against other tumor receptors.


The sequential changes in pancreatic exocrine function after abdominal surgery in the rat.
The sequential changes in pancreatic secretion in the conscious rat after pancreatic and intestinal surgery were examined. Rats were prepared with two duodenal cannulae and one cannula each for the pancreas, bile, and jugular vein. Pancreatic responses to Trasylol infused intraduodenally, bile-pancreatic juice (BPJ) diversion, and exogenous secretin and cerulein administrations were determined every 24 h after the operation. The body weight significantly decreased during the first 24 h after the operation but remained constant thereafter. The basal protein output was significantly lower on the first and second postoperative days compared with values on the third through seventh days, although the fluid output was almost constant throughout the observation period. Intraduodenal infusion of Trasylol failed to stimulate pancreatic secretion on the first and second postoperative days. Pancreatic feedback responses to BPJ diversion were observed during the entire experimental period, but were attenuated during the first 3 days. Responses to exogenous secretin and cerulein were relatively unaffected by postoperative recovery time. Results suggest that the pancreas itself may recover sufficiently within 24 h after the operation to respond consistently to direct stimulation. However, considering the effects on basal secretion and the responses to intestinally mediated secretion, it appears best to wait at least 3 days after the operation before using these rats in experiments on pancreatic exocrine functions.


[Chemical composition of surface antigens in the pseudotubercular microbe].
Superficially-active complexes, having a toxic effect and promoting generalization of the infestation process in the animal organism have been isolated from the pseudotubercular microbe. The chemical composition of these biopolymers has been studied.


Genetic analysis of the Drosophila ellipsoid body neuropil: organization and development of the central complex.
The central complex is an important center for higher-order brain function in insects. It is an intricate neuropil composed of four substructures. Each substructure contains repeated neuronal elements which are connected by processes such that topography is maintained. Although the neuronal architecture has been described in several insects and the behavioral role investigated in various experiments, the exact function of this neuropil has proven elusive. To describe the architecture of the central complex, we study 15 enhancer-trap lines that label various ellipsoid body neuron types. We find evidence for restriction of gene expression that is correlated with specific neuronal types: such correlations suggest functional classifications as well. We show that some enhancer-trap patterns reveal a single ellipsoid body neuron type, while others label multiple types. We describe the development of the ellipsoid body neuropil in wild-type animals and propose developmental mechanisms based on animals displaying structural mutations of this neuropil. The experiments performed here demonstrate the degree of resolution possible from the analysis of enhancer-trap lines and form a useful library of tools for future structure/function studies of the ellipsoid body.


[International Classification for Nursing Practice: technological instrument for professional practice].
The use of information technologies are considered as instruments that can do that nursing practice becomes visible in health data, local, national and internationally, in way to influence the elaboration of health and education policies. The development of nursing classification systems is approached, with emphasis in the International Classification for Nursing Practice - ICNP, with technological instrument for professional practice, which has as one of the principal criteria for its construction to be sufficiently wide and sensitive to cultural diversity, so that it serves to the multiples purposes requested by the different countries where it will be used.


DSM outcomes of psychotic experiences and associated risk factors: 6-year follow-up study in a community-based sample.
Psychotic experiences (PEs) may predict a range of common, non-psychotic disorders as well as psychotic disorders. In this representative, general population-based cohort study, both psychotic and non-psychotic disorder outcomes of PE were analysed, as were potential moderators. Addresses were contacted in a multistage clustered probability sampling frame covering 11 districts and 302 neighbourhoods at baseline (n = 4011). Participants were interviewed with the Composite International Diagnostic Interview (CIDI) both at baseline and at 6-year follow-up. Participants with PE at baseline were clinically re-interviewed with the SCID-I at follow-up. The role of socio-demographics, characteristics of PE, co-occurrence of mood disorders and family history of mental disorders were tested in the association between baseline PE and follow-up diagnosis. In the participants with baseline PE, the psychotic disorder diagnosis rate at follow up was 7.0% - much lower than the rates of DSM-IV mood disorders without psychotic features (42.8%) and other non-psychotic disorders (24.1%). Within the group with baseline PE, female sex, lower socio-economic status, co-occurrence of mood disorders, family history of a mental disorder and persistence of PE predicted any follow-up DSM diagnosis. Furthermore, onset of psychotic v. non-psychotic disorder was predicted by younger age (15-30 years), co-presence of delusional and hallucinatory PE and family history of severe mental illness. The outcome of PE appears to be a consequence of baseline severity of multidimensional psychopathology and familial risk. It may be useful to consider PE as a risk indicator that has trans-diagnostic value.


Guidelines for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 16: bone graft extenders and substitutes.
Despite the large volume of animal data regarding the use of synthetic bone graft substitutes or extenders, there are very few data regarding the use of these substances for fusion in lumbar degenerative disease. The best available data indicate that rhBMP-2 is a viable alternative to autograft bone for interbody fusion procedures. This same substance may also be a viable alternative to autograft for PLF; however, definitive medical evidence is not yet available. There is little, if any, medical evidence to support the use of other biological agents at the present time. As promising new compounds are brought to market, well-designed cohort studies and randomized trials will be required to determine the actual usefulness of these compounds in clinical practice. It is important not to generalize the results obtained with one preparation or application to different preparations or applications. The use of synthetic calcium phosphate ceramics as graft extenders appears to be reasonable in certain situations. The medical evidence available regarding their use is limited and of poor quality. Further study will be required to establish their utility for use in spinal fusion.


Ssu72 protein mediates both poly(A)-coupled and poly(A)-independent termination of RNA polymerase II transcription.
Termination of transcription by RNA polymerase II (Pol II) is a poorly understood yet essential step in eukaryotic gene expression. Termination of pre-mRNA synthesis is coupled to recognition of RNA signals that direct cleavage and polyadenylation of the nascent transcript. Termination of nonpolyadenylated transcripts made by Pol II in the yeast Saccharomyces cerevisiae, including the small nuclear and small nucleolar RNAs, requires distinct RNA elements recognized by the Nrd1 protein and other factors. We have used genetic selection to characterize the terminator of the SNR13 snoRNA gene, revealing a bipartite structure consisting of an upstream element closely matching a Nrd1-binding sequence and a downstream element similar to a cleavage/polyadenylation signal. Genome-wide selection for factors influencing recogniton of the SNR13 terminator yielded mutations in the gene coding for the essential Pol II-binding protein Ssu72. Ssu72 has recently been found to associate with the pre-mRNA cleavage/polyadenylation machinery, and we find that an ssu72 mutation that disrupts Nrd1-dependent termination also results in deficient poly(A)-dependent termination. These findings extend the parallels between the two termination pathways and suggest that they share a common mechanism to signal Pol II termination.


Guidelines for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 2: assessment of functional outcome.
Functional disability secondary to acute low-back pain, chronic low-back pain, lumbar stenosis, and lumbar disc disease may be reliably and validly assessed using functional outcome surveys that are valid, reliable, and responsive. Outcome instruments supported by Class I and Class II medical evidence for the evaluation of low-back pain include the Spinal Stenosis Survey of Stucki, Waddell-Main, RMDQ, DPQ, QPDS, SIP, Million Scale, LBPR Scale, ODI, and CBSQ. Many of these outcome measures have been applied to patients who have been treated with lumbar fusion for degenerative lumbar disease and have proven to be valid and responsive; however, the reliability of these instruments has never been specifically assessed in the lumbar fusion patient population. Patient satisfaction surveys have been used to measure outcome following lumbar fusion. Their usefulness resides in their insight into patient attitudes toward the treatment experience but is limited because of their inability to measure responsiveness and the lack of information on their reliability.


Calcinosis in juvenile dermatomyositis: a possible role for the vitamin K-dependent protein matrix Gla protein.
The aims of the present study were to investigate whether the calcification inhibitor matrix Gla protein (MGP) is expressed in muscle biopsies of patients with juvenile dermatomyositis (JDM), and whether different forms of MGP are differentially expressed in JDM patients with and without subcutaneous calcifications. Muscle tissue from six JDM patients (three without calcinosis, two with calcinosis and one recently diagnosed patient), four patients with muscular dystrophy, three patients with IBM and five normal histological control subjects was used for immunohistochemistry staining using novel antibodies to different conformations of MGP. In the JDM patients, all forms of MGP [non-carboxylated MGP (ucMGP), carboxylated MGP (cMGP), non-phosphorylated MGP (serMGP) and phosphorylated MGP (pserMGP)] were more intensely stained in the perifascicular compared with the central muscle fibres. In addition, these MGP species were demonstrated in the pathological muscle fibres of IBM and dystrophy patients, but hardly in normal histological muscle tissue. In JDM patients with calcifications, only pserMGP was increased compared with those without calcifications. All forms of MGP were also found in various staining intensities in the microvasculature and macrophages of normal histological and disease biopsies. MGP was expressed at the site of muscle damage in JDM patients as well as in patients with muscular dystrophy and IBM. The difference in staining intensity of pserMGP appeared to distinguish between JDM patients with and without calcifications, whereas cMGP, the other functional form, was equally expressed.


The rise of global health diplomacy: An interdisciplinary concept linking health and international relations.
Global health diplomacy (GHD) is relatively a very new field that has yet to be clearly defined and developed though there are various definitions given by different experts from foreign policy, global health, diplomacy, international relations, governance, and law. With the intensification of globalization and increasing gaps between countries, new and reemerging health threats such as HIV/AIDS, tuberculosis, influenza, severe acute respiratory syndrome, Ebola, and Zika and a gradual rethinking on security concepts framed a new political context. The health problems addressed diplomatically have also become diverse ranging from neglected tropical diseases, infectious diseases, sale of unsafe, counterfeit drugs to brain drain crisis. We see that global health has become more diverse as the actors widened and also the interests appealing not only to the traditional humanitarian ideals associated with health but also to the principles grounded in national and global security. Recently, we are witnessing the increased priority given to the GHD because the issue of health is discussed by various actors outside the WHO to shape the global policy for health determinants. In fact, the area of health has become the part of UN Summit Diplomacy involving the G8, G20, BRICS, and the EU. The recent WHO Pandemic Influenza Framework, UN High Level Framework on Prevention and Control of Noncommunicable Diseases, and the WHO Framework Convention on Tobacco Control are some of the examples of long-term negotiation processes for agreements that took place.


Modulating Sticking Propensity of Pharmaceuticals Through Excipient Selection in a Direct Compression Tablet Formulation.
To investigate how excipient matrix affects punch sticking propensity of active pharmaceutical ingredients (API), with the focus on the effect of bonding interactions between API-API (F2) and API-excipient (F3). Sticking kinetics of direct compression formulations, consisting of 20% of celecoxib (CEL) or ibuprofen (IBN) in different excipient matrices, i.e., microcrystalline cellulose (Avicel PH102 and Avicel PH105 dry coated with nano-sized silica (PH105(n)), hypromellose (K15 M), and a 3:1 mixture between starch and Avicel PH102 (S3P1), was assessed using a removable punch tip on a compaction simulator. The amount of material transferred to punch was determined gravimetrically every 10 compressions up to 50 compactions. CEL exhibited higher F2 than IBN. CEL also exhibited more sticking under otherwise identical compaction conditions in the same excipient matrix. Among different excipient matrices, sticking propensity of both APIs followed the ascending order: PH105(n) < PH102 < K15 M < S3P1. This order was exactly opposite to the order of F3, confirming that greater bonding strength of the formulation favors lower sticking propensity of a given API. For an API prone to punch sticking, judicious use of excipients to render higher tablet mechanical strength can mitigate severity of punch sticking.


Recent developments in the kinetics of ruptures of giant vesicles under constant tension.
External tension in membranes plays a vital role in numerous physiological and physicochemical phenomena. In this review, recent developments in the constant electric- and mechanical-tension-induced rupture of giant unilamellar vesicles (GUVs) are considered. We summarize the results relating to the kinetics of GUV rupture as a function of membrane surface charge, ions in the bathing solution, lipid composition, cholesterol content in the membrane, and osmotic pressure. The mechanical stability and line tension of the membrane under these conditions are discussed. The membrane tension due to osmotic pressure and the critical tension of rupture for various membrane compositions are also discussed. The results and their analysis provide a biophysical description of the kinetics of rupture, along with insight into biological processes. Future directions and possible developments in this research area are included.


Methods for the assessment of the effects of drugs on coronary blood flow in man.
The methods currently available for measurement of coronary blood flow in man are reviewed and their advantages and limitations discussed. Most of the techniques are invasive and involve cardiac catheterization. The least invasive isotope techniques are either not quantitative or involve expensive equipment not available in many centres. Two of the most suitable methods for assessing the effects of drugs on coronary flow are coronary sinus thermodilution and isotope washout curves using 133xenon or [125I]-iodo-antipyrine. The ideal technique for measuring coronary blood flow has yet to be developed.


[Acute ischemia of the lesser gastric curvature--a rare marker of sclerotic disease].
The rich blood supply of the stomach protects it from ischemia and necrosis. Acute gastric ischemia, an emergency with high mortality, is rare. Atherosclerosis is the leading cause of acute ischemia, and the lesser curvature of the stomach is more vulnerable due to its relatively lesser blood supply. Reduction in gastric blood supply usually presents as chronic disease characterized by gastritis, gastric ulcer, or gastroparesis. Gastroscopy can identify lesions of the gastric mucosa, and angiography demonstrates occluded vessels. Treatment of acute gastric ischemia is surgical, with total gastrectomy preferred over partial resection.


Fibrin in peritonitis. III. The mechanism of bacterial trapping by polymerizing fibrin.
We have previously shown that fibrin can act to contain microorganisms and prevent early septic death in experimental peritonitis. However, this trapping eventuates in abscess formation. Fibrinogen, the precursor molecule of fibrin, is known to possess binding structures for some pathogenic organisms. We compared the extent of incorporation of various aerobic and anaerobic bacteria as well as polystyrene latex microspheres into fibrin clots. Similar numbers of organisms and microspheres were incorporated into either noncontracted or contracted fibrin clots. Detailed comparisons of the binding of Escherichia coli or Staphylococcus aureus to human fibrinogen were then made. The addition of 111:B4 lipopolysaccharide did not inhibit incorporation of E. coli 0111:B4 into either type of fibrin clot. With initial inoculum sizes of 10(6) to 10(8) colony-forming units (CFU)/ml, S. aureus was better incorporated into contracted fibrin clots (P less than 0.01) than was E. coli, possible evidence for an easily saturable receptor mechanism. We concluded that microorganisms are incorporated into the polymerizing fibrin matrix in the same fashion as are inert particles of similar size, irrespective of external chemical structure. Adherence of bacteria to fibrinogen or polymerizing fibrin did not appear to represent a specific bacterial virulence factor, more likely representing an effective host defense mechanism of broad specificity.


Correlation of electrophoretic urine protein banding patterns with severity of renal damage in dogs with proteinuric chronic kidney disease.
Urine protein loss is common in dogs with chronic kidney disease (CKD). Currently available noninvasive means of evaluating CKD in dogs cannot accurately predict the severity of glomerular and tubulointerstitial damage. Electrophoretic analysis of urine proteins can indicate the compromised renal compartment (glomerular vs tubular), but extensive evaluation of protein banding pattern associations with histologic damage severity has not been performed in dogs. We aimed to evaluate electrophoretic banding patterns as indicators of the presence and severity of glomerular and tubulointerstitial damage in dogs with naturally occurring, predominantly proteinuric CKD. We performed a retrospective study using urine and renal tissue from 207 dogs with CKD. Urine protein banding patterns were correlated with histologic severity of renal damage. Sensitivity and specificity of banding patterns for the detection of glomerular and tubulointerstitial damage were determined. Banding patterns were 97% sensitive and 100% specific for the detection of glomerular damage and 90% sensitive and 100% specific for the detection of tubulointerstitial damage. Correlations between composite banding patterns and the severity of renal damage were strong, while glomerular banding patterns correlated moderately with glomerular damage severity, and tubular gel scores correlated weakly to moderately with the severity of tubulointerstitial damage. Urine protein banding patterns are useful for the detection of glomerular and tubulointerstitial damage in dogs with proteinuric CKD.


We don't train in vain: a dissemination trial of three strategies of training clinicians in cognitive-behavioral therapy.
There has been little research on the effectiveness of different training strategies or the impact of exposure to treatment manuals alone on clinicians' ability to effectively implement empirically supported therapies. Seventy-eight community-based clinicians were assigned to 1 of 3 training conditions: review of a cognitive-behavioral therapy (CBT) manual only, review of the manual plus access to a CBT training Web site, or review of the manual plus a didactic seminar followed by supervised casework. The primary outcome measure was the clinicians' ability to demonstrate key CBT interventions, as assessed by independent ratings of structured role plays. Statistically significant differences favoring the seminar plus supervision over the manual only condition were found for adherence and skill ratings for 2 of the 3 role plays, with intermediate scores for the Web condition.


1,4-Dihydropyridyl complexes of magnesium: synthesis by pyridine insertion into the magnesium-silicon bond of triphenylsilyls and catalytic pyridine hydrofunctionalization.
Magnesium bis(triphenylsilyl) [Mg(SiPh3)2(THF)2]·THF (1) reacted with a stoichiometric amount of pyridine to give the magnesium 4-(triphenylsilyl)dihydropyridyl complex [Mg(NC5H5-4-SiPh3)2(THF)3] (2). Using an excess of pyridine, a mixture of magnesium dihydropyridyl [Mg(NC5H6)2(py)4] (3) and 4-(triphenylsilyl)pyridine was formed. Complex 3 underwent exchange with pyridine-d5 at 25 °C to give [Mg(NC5D5H-4)2(py-d5)4] (3-HD). Analogous reactions with Me3TACD-supported magnesium triphenylsilyls [(Me3TACD)Mg(SiPh3)] (4) and [(Me3TACD·AlEt3)Mg(SiPh3)] (6) ((Me3TACD)H = Me3[12]aneN4: 1,4,7-trimethyl-1,4,7,10-tetraazacyclododecane) with pyridine gave [(Me3TACD)Mg(NC5H5-4-SiPh3)] (5), [(Me3TACD·AlEt3)Mg(NC5H5-4-SiPh3)] (7) and a mixture of [(Me3TACD)Mg(NC5H6)] (8) and 4-(triphenylsilyl)pyridine. Complex 8 is also formed by reacting 3 with (Me3TACD)H and underwent exchange with pyridine-d5 at higher temperatures. The activation energy for the exchange is about 25 kJ mol-1 higher than that for the exchange reaction of 3 to 3-HD. Complexes 2, 3, 3-HD, 5, 7 and 8 were characterized by NMR spectroscopy and 3, 5 and 8 by single crystal structure analysis. Complex 3 was found to be slightly active in the hydrosilylation of pyridine using phenylsilane, whereas complex 8 showed no activity. Both complexes 3 and 8 were active in the hydroboration of pyridine with pinacolborane.


BMP-2 Variants in Breast Epithelial to Mesenchymal Transition and Microcalcifications Origin.
This study aims to investigate the possible different roles of the BMP-2 variants, cytoplasmic and nuclear variant, in both epithelial to mesenchymal transition and in microcalcifications origin in human breast cancers. To this end, the in situ expression of cytoplasmic and nuclear BMP-2 was associated with the expression of the main epithelial to mesenchymal transition biomarkers (e-cadherin and vimentin) and molecules involved in bone metabolisms (RUNX2, RANKL, SDF-1) by immunohistochemistry. In addition, the expression of cytoplasmic and nuclear BMP-2 was associated with the presence of microcalcifications. Our data showed a significant association among the number of cytoplasmic BMP-2-positive cells and the number of both vimentin (positive association) and e-cadherin (negative association) positive breast cells. Conversely, no associations were found concerning the nuclear BMP-2-positive breast cells. Surprisingly, the opposite result was obtained by analyzing the variants of BMP-2 and both the expression of RANKL and SDF-1 and the presence of microcalcifications. Specifically, the presence of microcalcifications was related to the expression of nuclear BMP-2 variant rather than the cytoplasmic one, as well as a strong association between the number of nuclear BMP-2 and the expression of the main breast osteoblast-like cells (BOLCs) biomarkers. To further corroborate these data, an in vitro experiment for demonstrating the co-expression of nBMP-2 and RANKL or vimentin or SDF-1 in breast cancer cells that acquire the capability to produce microcalcifications was developed. These investigations confirmed the association between the nBMP-2 expression and both RANKL and SDF-1. The data supports the idea that whilst cytoplasmic BMP-2 can be involved in epithelial to mesenchymal transition phenomenon, the nuclear variant is related to the essential mechanisms for the formation of breast microcalcifications. In conclusion, from these experimental and translational perspectives, the complexity of BMP-2 signaling will require a detailed understanding of the involvement of specific BMP-2 variants in breast cancers.


Utilization of growth monitoring and promotion services among children younger than 2 years in West Armachiho district, Northwest Ethiopia.
Inadequate physical growth and poor development of children are prevalent and significant problems worldwide, with 149 million children younger than 5 years stunted and 49 million wasted. Growth monitoring and promotion (GMP) is one of the major activities implemented with the aim of capturing growth faltering before the child reaches the status of undernutrition. In relation to this, the Amhara region, where the study area is found, is a highly burdened area for child malnutrition. Thus, it needs further investigation about the utilization of GMP services and associated factors among children younger than 2 years in the study area. The aim of this study was to assess the utilization of growth monitoring and promotion services and associated factors among children younger than 2 years. A community-based cross-sectional study was conducted in the West Armachiho district, including 703 mother-child pairs, with a response rate of 94.7%. A simple random sampling technique was used to select the respondents. Both bivariable and multivariable logistic regression analyzes were performed. An adjusted odds ratio (AOR) with a 95% confidence interval was used to measure the strength of the association. The proportion of utilization of growth monitoring and promotion services in the West Armachiho district was 13.7% (95%Cl; 11.2, 16.4). Factors such as maternal educational status (AOR = 2.17, 95%Cl; 1.05, 4.49), institutional delivery (AOR = 3.16, 95%Cl; 1.62, 6.13), family size (AOR = 2.66, 95%Cl; 1.13, 6.23), access to health facility (AOR = 3.17, 95%Cl; 1.45, 6.95), and maternal knowledge (AOR = 4.53, 95%Cl; 2.71, 7.59) were significantly associated with the utilization of growth monitoring and promotion services. Utilization of growth monitoring and promotion services in children younger than 2 years in the West Armachiho district was low. Thus, giving due attention to the improvement of the knowledge of the mothers/caregivers about child GMP services and counseling them about the importance of facility delivery is vital to improving growth monitoring and promotion services in the area.


Bile acid pneumonia: a "new" form of neonatal respiratory distress syndrome?
We describe 3 cases of neonatal respiratory distress syndrome (RDS) in near-term infants, born from mothers with severe intrahepatic cholestasis of pregnancy. Common pictures of the cases were: good indices of lung maturity in the amniotic fluid; severe RDS requiring mechanical ventilation; high serum bile acid (BA) levels in the early days of life; no meconium aspiration; negative cultures; and absence of indirect laboratory signs of infection. After the first case, we hypothesized that abnormally high BA levels could have reversed the action of phospholipase A2 in the lungs, causing a degradation of phosphatidylcholines to lysophosphatidylcholines and the consequent lack of surfactant activity, leading to the severe respiratory distress. Consequently, in cases 2 and 3, we gave intratracheal surfactant to the infants, which, although administered around the first 24 hours of life, showed to be helpful. Our experience suggests that a high level of attention in the management of newborn infants (even near-term infants) born from women with intrahepatic cholestasis of pregnancy is necessary to detect as soon as possible signs and symptoms of this "unexpected" RDS, which can assume a very severe clinical picture. In such instances, we recommend that the diagnosis of BA pneumonia be kept in mind and that exogenous surfactant be given as soon as possible, even in the presence of indices of normal lung maturity in the amniotic fluid. Finding high levels of BA and lysophosphatidylcholines in the bronchoalveolar lavage of affected infants would aid in support of the diagnosis.


Mitochondrial permeability transition in acetaminophen-induced necrosis and apoptosis of cultured mouse hepatocytes.
Acetaminophen overdose causes massive hepatic failure via mechanisms involving glutathione depletion, oxidative stress, and mitochondrial dysfunction. The ultimate target of acetaminophen causing cell death remains uncertain, and the role of apoptosis in acetaminophen-induced cell killing is still controversial. Our aim was to evaluate the mitochondrial permeability transition (MPT) as a key factor in acetaminophen-induced necrotic and apoptotic killing of primary cultured mouse hepatocytes. After administration of 10 mmol/L acetaminophen, necrotic killing increased to more than 49% and 74%, respectively, after 6 and 16 hours. MPT inhibitors, cyclosporin A (CsA), and NIM811 temporarily decreased necrotic killing after 6 hours to 26%, but cytoprotection was lost after 16 hours. Confocal microscopy revealed mitochondrial depolarization and inner membrane permeabilization approximately 4.5 hours after acetaminophen administration. CsA delayed these changes, indicative of the MPT, to approximately 11 hours after acetaminophen administration. Apoptosis indicated by nuclear changes, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and caspase-3 activation also increased after acetaminophen administration. Fructose (20 mmol/L, an adenosine triphosphate-generating glycolytic substrate) plus glycine (5 mmol/L, a membrane stabilizing amino acid) prevented nearly all necrotic cell killing but paradoxically increased apoptosis from 37% to 59% after 16 hours. In the presence of fructose plus glycine, CsA decreased apoptosis and delayed but did not prevent the MPT. In conclusion, after acetaminophen a CsA-sensitive MPT occurred after 3 to 6 hours followed by a CsA-insensitive MPT 9 to 16 hours after acetaminophen. The MPT then induces ATP depletion-dependent necrosis or caspase-dependent apoptosis as determined, in part, by ATP availability from glycolysis.


Human urinary bladder smooth muscle is dependent on membrane cholesterol for cholinergic activation.
Voiding is mediated by muscarinic receptors in urinary bladder smooth muscle cells. Lipid rafts and caveolae are cholesterol enriched membrane domains that modulate the activity of G protein-coupled receptors and second messenger systems. Conflicting findings regarding sensitivity of muscarinic signalling to cholesterol desorption, which perturbs lipid rafts and caveolae, have been reported, and no study has used human urinary bladder. Here, the dependence of human bladder muscarinic receptor signalling on plasma membrane cholesterol was examined. Nerve-mediated contraction, elicited by electrical field stimulation of human bladder strips, was impaired by desorption of cholesterol using methyl-beta-cyclodextrin, and the concentration-response curve for the muscarinic agonist carbachol was right-shifted. No effect of cholesterol desorption was observed in rat, and in mouse increased maximum contraction was seen. Expression of caveolin-1, PLCbeta1 and M3 muscarinic receptors did not differ between species in a manner that would explain the differential sensitivity to cholesterol desorption. In human bladder, threshold depolarisation eliminated the difference between cyclodextrin-treated and control preparations. Contraction elicited by depolarisation per se was not affected. M3 muscarinic receptors appeared clustered along plasma membrane profiles as shown by immunohistochemical staining of human bladder, but no redistribution in association with cholesterol reduction was seen. Thus, muscarinic receptor-induced contraction of the urinary bladder exhibits species-specific differences in its sensitivity to cholesterol desorption suggesting differential roles of lipid rafts/caveolae in muscarinic receptor signalling between species.


Irritable bowel syndrome in Indonesian adolescents.
Irritable bowel syndrome is a frequent functional gastrointestinal disorder. The aims of this study were to investigate its epidemiology, focusing on the role of intestinal mucosal integrity and to evaluate the impact on the quality of life. A community-based survey applying a comparative cross sectional approach was conducted in six high schools in Palembang. Subjects were recruited using multistage random sampling divided in two groups. Rome III criteria were used to establish a diagnosis of IBS in combination with a questionnaire to determine risk factors. Determination of fecal alpha-1-antitrypsin and calprotectin levels was performed to determine impaired intestinal mucosal integrity. A questionnaire was used to evaluate how quality of life was affected by irritable bowel syndrome. The survey was performed in 454 14-18years old adolescents, of whom 30.2% fulfilled the Rome III criteria for IBS, with the following subtypes: 36.5% diarrhea, 18.9% constipation, 21.9% mixed, and 22.6% unclassified. Major risk factors were female gender, bullying, age 14-16 years, history of constipation and diarrhea, eating nuts, and drinking coffee, tea, and soft drinks. There was a significant association with intestinal inflammation (p=0.013). A significantly impaired quality of life was found (p=0.001). The prevalence of irritable bowel syndrome in adolescents was high, with bullying, female gender, age 14-16 years, constipation and diarrhea, and dietary consumption of soft drinks, coffee, and tea as risk factors. A significant association with intestinal inflammation was found.


Safety and immunogenicity of immunotherapy with polymerized tree, grass, and ragweed in patients with multiple inhalant sensitivities.
Immunotherapy with polymerized ragweed (PRW) and individually polymerized grasses (IPG) previously has been demonstrated to be safe and effective. We conducted this trial in order to assess safety and immunogenicity of individually polymerized trees (IPT) and to assess safety of concomitantly administering IPT, IPG, and PRW in patients with multiple inhalant sensitivities. Sixteen patients with typical tree pollinosis were recruited; all but one had grass pollinosis, and all had ragweed pollinosis. Patients were treated in 12 weekly visits with allergens to which they were sensitive, 48,850 PNU of IPT; 2668 AU (50,000 PNU) of PRW; and 48,850 PNU of IPG. There were no systemic reactions and no changes in laboratory parameters, including renal and hepatic functions with injections. Blood was drawn for immunologic studies before and after the injection series. There were significant rises in IgG titers by ELISA to each tree allergen administered, oak, elm, and box elder. There were significant rises in total antibody binding of ragweed AgE and rye grass group I in patients treated with PRW and IPG, respectively. Changes in IgE to oak, elm, box elder, AgE, and rye grass group I were minimal. In summary, IPT is safe, immunogenic, and can be administered concomitantly with PRW and IPG in patients with multiple inhalant sensitivities.


[Method of determining the antibiotic sensitivity of anaerobic microorganisms using standard disks].
Three variants of the procedure for determination of antibiotic sensitivity in anaerobic microorganisms with the use of standard paper discs were developed. According to the first variant the solid nutrient medium is melted at 46 degrees C and mixed with the culture of the microbe being tested. The mixture is added to the cover of a Petri dish. When the medium becomes solid, antibiotic sensitivity discs are placed onto the agar surface. After that one more layer of the medium is added. The medium is allowed to solidify and some more medium is poured near the cover edge. Immediately after that the Petri dish is placed with its flat surface onto the agar layer in its cover. According to the first and second variants the mixture of the medium and culture is added to a Petri dish and immediately a transparent gas-proof polymer film of the dish size is placed onto the agar surface. Previously antibiotic paper discs or solutions are fixed on the films. THe incubation temperature for all three variants is 37 degrees C. The procedure allows one to observe the culture growth and to obtain the results earlier than in case the culture is incubated in an aerostate. The procedure is simple and saves labor and time.


Cyberphysical Human Sexual Behavior Acquisition System (SeBA): Development and Implementation Study in China.
Sexual health is one of the principal components of human well-being. Traditional methods for observing human sexual behavior typically adopt manual intervention approaches (eg, interviews). However, the data obtained by such traditional approaches suffer from intrinsic bias and limited sample sizes. Sexual behavioral data that are more reflective of the actual situation can be collected by equipping sex toys with sensors. To address the limitations of traditional human sexual behavior data observation methods, a novel cyberphysical system is proposed to capture natural human sexual behavior data in China at the nationwide level. A cyberphysical human sexual behavior acquisition system (SeBA) was designed and implemented. SeBA jointly utilizes state of the art information and communication technologies such as smart sex toys, smartphones, and mobile social networks. Smart sex toys enable objective collection of data on human sexual behavior, while the mobile social network provides the possibility of partnered sex in a cyberphysical manner. The objectives and function settings are discussed, and the overall framework of the system architecture is presented. Operation and privacy policies are proposed and the technical solution of SeBA is described. The effectiveness of SeBA was verified based on analysis of users' human sexual behavior data collected from January 2016 to June 2017. A total of 103,424 solo sexual behaviors were recorded involving 13,047 users, and 61,007 partnered sexual behaviors from 7,140 users were observed. The proportions of males and females in the solo and partnered sex groups were fairly consistent with recent statistics on unmarried individuals in China. We also found that only a small portion of individuals provided information on at least one other attribute besides the required input of gender, such as age, height, location, job, sex preferences, purposes, and interests. To the best of our knowledge, this is the first study to analyze objective human sexual behavior data at the nationwide level. Although the data are restricted to China, this study can provide insight for further research on human sexual behavior based on the huge amount of data available from wireless smart sex toys worldwide. It is anticipated that findings from such objective big data analyses can help deepen our understanding of sexual behavior, as well as improve sexual health and sexual wellness.


Trajectories describing the evolution of polarized light in homogeneous anisotropic media and liquid crystals.
Trajectories are given that describe the evolution of the ellipse of polarization in the complex plane for light propagating in a homogeneous anisotropic medium and along the helical axis of a cholesteric liquid crystal. For the general homogeneous anisotropic medium that exhibits combined birefringence and dichroism the trajectory is a spiral that converges to the low-absorption eigenpolarization. For pure birefringence the trajectory becomes a complete circle that encloses one eigenpolarization, whereas for pure dichroism the trajectory becomes an arc of a circle that ends at the low-absorption eigenstate. The case of a cholesteric (or twisted nematic) liquid crystal leads to an interesting family of trajectories that can be considered as distorted hypo- or epicycloids. These trajectories are nonrepetitive (open) and may show multilobes or branches depending upon the initial polarization and the properties of the liquid crystal. Graphs are also presented where the ellipticity and azimuth are plotted separately as functions of distance along the helical axis.


Universal features of counting statistics of thermal and quantum phase slips in nanosize superconducting circuits.
We perform measurements of phase-slip-induced switching current events on different types of superconducting weak links and systematically study statistical properties of the switching current distributions. We employ two types of devices in which a weak link is formed either by a superconducting nanowire or by a graphene flake subject to proximity effect. We demonstrate that independently of the nature of the weak link, higher moments of the distribution take universal values. In particular, the third moment (skewness) of the distribution is close to -1 both in thermal and quantum regimes. The fourth moment (kurtosis) also takes a universal value close to 5. The discovered universality of skewness and kurtosis is confirmed by an analytical model. Our numerical analysis shows that introduction of extraneous noise into the system leads to significant deviations from the universal values. We suggest using the discovered universality of higher moments as a robust tool for checking against undesirable effects on noise in various types of measurements.