Relationship of percutaneous endoscopic gastrostomy-related mortality and morbidity rates and effectiveness with advancing age.
Percutaneous endoscopic gastrostomy (PEG) is insertion of a tube to stomach through abdominal wall for provision of nutrition in patients who couldn't be fed by oral route. In the present study, it was aimed to evaluate PEG procedures performed in our facility regarding indication, complication and effectiveness and to determine whether these characteristics have a relationship with advancing age. In this descriptive study, we reviewed clinical and endoscopic records of 300 patients who underwent PEG procedure between May 2009 and December 2011. The patients were divided into 2 groups(group 1 > 75, group 2 < 75 years). All patients were retrospectively reviewed regarding demographic data, indications, biochemical parameters (Hemoglobin, total protein and albumin) at baseline and 3 months after procedure, complications and mortality. The most common indication for PEG was neurological (67.3%). Wound infection (6.0%) was most common early complication while tube occlusion (4.7%) was most common late complication. No significant difference was detected between groups regarding morbidity and mortality (p < 0.05). It was seen that there were significant improvement in all biochemical parameters (p < 0.001). The most significant improvement was observed in total protein values (p < 0.05). However, no significant difference was detected in individual parameters (p > 0.05). PEG should be preferred at early period in patients who couldn't be fed by oral route for prolonged time as it is a minimally invasive, simple, inexpensive, highly effective, physiologic and safe. PEG was found to have no relationship with advancing age regarding indications, morbidity, mortality rate and effectiveness.


Estrogen and progestin receptor levels in uterine leiomyomata: relation to the tumour histology and the phase of menstrual cycle.
Estrogen receptor (ER) and progestin receptor (PR) levels in the myometria and uterine leiomyomata of 26 normally menstruating women were studied. No significant menstrual cycle-related change in ER level was found in the leiomyomata or normal myometria. The ER levels in normal myometria and in cellular leiomyomata, but not in usual leiomyomata, tended to be higher in the follicular phase than in the luteal one. The "cytosolic" PR levels in cellular leiomyomata and in usual leiomyomata with no or with slight hyalinization as well as in their parental myometria were significantly lower in the luteal than in the follicular phase. This was not the case in usual leiomyomata with more intense hyalinization. The findings show that the reactivity of uterine leiomyomata to estrogens and/or progestins may be related to the histological features of the tumors. This should be realized when studying the steroid receptor levels in the tumours and possibly also when planning an endocrine therapy for the leiomyomata.


The heme oxygenase inducer hemin protects against cardiac dysfunction and ventricular fibrillation in ischaemic/reperfused rat hearts: role of connexin 43.
Cardiac expression of cytoprotective gene heme oxygenase-1 (HO-1) is modulated by ischaemia and reperfusion (I/R). We therefore hypothesized that pretreatment with hemin, an inductor of HO-1, would precondition the heart against post-ischaemic dysfunction and ventricular fibrillation (VF). Male Wistar rats were given either hemin or HO enzyme inhibitor zinc protoporphyrin IX (ZnPP IX). Isolated hearts were subjected to 30 min global ischaemia followed by 120 min of reperfusion or were aerobically perfused in a time-matched non-ischaemic protocol. Control animals received no pretreatment. Compared to non-perfused controls, pretreatment with hemin increased HO-1 mRNA 13-fold (p<0.001) and HO-1 protein 3.5-fold (p<or=0.001), improved post-ischaemic aortic flow, coronary flow, LVDP and -Dp/dt (p<0.01) and decreased LVEDP (p<0.001) and the incidence of VF (p = 0.001). The improved post-ischaemic cardiac function and reduction of VF were accompanied by a higher total connexin 43 (Cx43) level compared to non-pretreated and ZnPP IX pretreated hearts, and accumulation of non-phosphorylated gap junction protein Cx43 in intercalated discs and lateral plasma membrane of cardiomyocytes. Cardioprotection by HO-1 appeared to be independent of cGMP. Administration of ZnPP IX had no effect on cardiac function or VF. Our results show that pharmacological modulation of HO-1 pathway may provide a new therapeutic approach to protect the heart against post-ischaemic dysfunction and I/R-induced VF possibly by a Cx43 dependent mechanism.


Interaction of chronic total occlusion and chronic kidney disease in patients undergoing primary percutaneous coronary intervention for acute ST-elevation myocardial infarction.
Chronic total occlusion (CTO) in a non-infarct-related artery and chronic kidney failure (CKD) are associated with worse outcomes after primary percutaneous coronary intervention (PCI). The aim of this study was to investigate the interaction of CTO and CKD in patients who underwent primary PCI for acute ST-segment elevation myocardial infarction (STEMI). Patients with STEMIs with or without CKD, defined as an estimated glomerular filtration rate <60 ml/min/1.73 m(2), were categorized into those with single-vessel disease and those with multivessel disease with or without CTO. The primary outcomes were the incidence of 30-day and 1-year mortality. Among 1,873 consecutive patients with STEMIs included between 2006 and 2011, 336 (18%) had CKD. The prevalence of CTO in a non-infarct-related artery was 13% in patients with CKD compared with 7% in those without CKD (p = 0.0003). There was a significant interaction between CKD and CTO on 30-day mortality (p = 0.018) and 1-year mortality (p = 0.013). Independent predictors of late mortality in patients with CKD were previous myocardial infarction (hazard ratio [HR] 1.71, 95% confidence interval [CI] 1.01 to 2.79), age >75 years (HR 1.86, 95% CI 1.19 to 2.95), a left ventricular ejection fraction after primary PCI <40% (HR 2.20, 95% CI 1.36 to 3.63), left main culprit artery (HR 4.46, 95% CI 1.64 to 10.25), and shock (HR 7.44, 95% CI 4.56 to 12.31), but multivessel disease with CTO was not a predictor. In contrast, multivessel disease with CTO was an independent predictor of mortality in patients without CKD (HR 3.30, 95% CI 1.70 to 6.17). In conclusion, in patients with STEMIs who underwent primary PCI, with preexisting CKD, the prevalence of CTO in a non-infarct-related artery was twice as great. In these patients, the clinical impact of CTO seems to be overshadowed by the presence of CKD.


Peptides in Parkinson's disease.
Peptides have found a progressively more important role in the biochemistry and physiology of the brain in recent years. Many possess neurological and behavioral actions in addition to their function in endocrinology. This paper reviews the formation and distribution, as well as the neurological action, of peptides probably involved in Parkinson's disease: beta-LPH and its derivatives (MSH, ACTH4-10, beta-endorphin). It also recounts the experience of many authors with prolyl-leucyl-glycine-amide (PLG) in that disease. Finally we propose a new theory of the etiology of Parkinson's disease, based on a postulated deficiency in the important trophic function upon catecholaminergic neurons of A.P.U.D. cells.


Drugs in hair: a new extraction procedure.
An enzymatic hydrolysis of hair for drug detection is described. The results obtained with the suggested method are compared with those observed by chemical hydrolysis. Enzymatic digestion provides a high recovery (80%) for cocaine metabolite, while alkaline hydrolysis causes its chemical destruction. The two hydrolytic procedures yielded comparable results for morphine. The outlined procedure is recommended when unstable compounds are to be detected in hair.


Accurate mass-time tag library for LC/MS-based metabolite profiling of medicinal plants.
We report the development and testing of an accurate mass-time (AMT) tag approach for the LC/MS-based identification of plant natural products (PNPs) in complex extracts. An AMT tag library was developed for approximately 500 PNPs with diverse chemical structures, detected in electrospray and atmospheric pressure chemical ionization modes (both positive and negative polarities). In addition, to enable peak annotations with high confidence, MS/MS spectra were acquired with three different fragmentation energies. The LC/MS and MS/MS data sets were integrated into online spectral search tools and repositories (Spektraris and MassBank), thus allowing users to interrogate their own data sets for the potential presence of PNPs. The utility of the AMT tag library approach is demonstrated by the detection and annotation of active principles in 27 different medicinal plant species with diverse chemical constituents.


Multiple anterograde and retrograde AV nodal pathways: demonstration by multiple discontinuities in the AV nodal conduction curves and echo time intervals.
Programmed electrical cardiac stimulation was performed in a 40-year-old man with documented recurrent, sustained ventricular tachycardia which was refractory to standard medical therapy. Both the presence of several discontinuities in the AV nodal conduction curves during atrial and ventricular stimulation and the time intervals of the AV nodal echo phenomena suggested the presence of multiple AV nodal pathways. The results of this study are of interest in further increasing our understanding of the electrophysiologic behavior of the human AV node.


Unsaturated trinuclear iron fluoroborylene complexes.
The unsaturated trinuclear iron fluoroborylene complexes Fe3(BF)3(CO) n (n = 7, 6) have been studied using density functional theory (DFT). Relatively complicated potential energy surfaces are found with nine and eight structures within 15 kcal mol-1 of the lowest energy structures for the Fe3(BF)3(CO)7 and Fe3(BF)3(CO)6 systems, respectively. In each of these low-energy structures all three BF groups are either edge-bridging or face-bridging but never terminal groups. Some, but not all, of the low-energy structures also have edge-bridging and/or face-bridging CO groups leading to some structures with as many as five bridging groups. The relatively narrow range of Fe-Fe distances in the central Fe3 triangles of the Fe3(BF)3(CO) n (n = 7, 6) structures, mainly between 2.37 and 2.55 Å, suggests considerable delocalization in these unsaturated systems. Graphical Abstract The lowest energy Fe3(BF)3(CO)7 and Fe3(BF)3(CO)6 structures have a face-bridging μ3-BF group with the two remaining BF groups bridging edges. The lowest energy Fe3(BF)3(CO)6 structure also has one four-electron donor bridging η2-μ-CO group.


Standardization of (55)Fe by tracing method.
This work describes the procedure followed by the Laboratório de Metrologia Nuclear (LMN) for the standardization of (55)Fe by the tracing method. This technique was applied using two radionuclides, which decay by the electron capture process followed by a prompt gamma-ray, namely (51)Cr and (54)Mn, as tracers. The calibration was performed in a 4pibeta-gamma coincidence system. The efficiency was obtained by selecting a gamma-ray window set at the 320keV total absorption peak for (51)Cr and at 834keV for (54)Mn.


Application of Machine Learning Algorithms to Metadynamics for the Elucidation of the Binding Modes and Free Energy Landscape of Drug/Target Interactions: a Case Study.
In the context of drug discovery, computational methods were able to accelerate the challenging process of designing and optimizing a new drug candidate. Amongst the possible atomistic simulation approaches, metadynamics (metaD) has proven very powerful. However, the choice of collective variables (CVs) is not trivial for complex systems. To automate the process of CVs identification, two different machine learning algorithms were applied in this study, namely DeepLDA and Autoencoder, to the metaD simulation of a well-researched drug/target complex, consisting in a pharmacologically relevant non-canonical DNA secondary structure (G-quadruplex) and a metallodrug acting as its stabilizer, as well as solvent molecules.


Cytochrome f and plastocyanin kinetics in Chlorella pyrenoidosa. II. Reduction kinetics and electric field increase in the 10 ms range.
On dark-adapted Chlorella, after one flash, plastocyanin (PC) undergoes reduction with a half-time of 7 ms. After 4 or 5 flashes, the reduction of PC+ in the 10 ms range is suppressed, and the level of oxidized plastocyanin increases during the next few flashes before reaching a stationary value. Cytochrome f exhibits approximately the same pattern. The reduction of PC+ and cytochrome f+ in the 10 ms range is correlated with an increase of the electrice field named phase b (Joliot, P. and Delosme, R., Biochim. Biophys. Acta 357 (1974) 267-284). Both need the presence of a compound R' in the reduced state. A dark electron transfer involving a carrier of electrons across the membrane, a proton carrier, R' as terminal reducant, PC+ and cytochrome f+ as terminal oxidants, would account for this field generation. Cooperation between the electron transfer chains is implied at the level of plastocyanin oxidation. An equilibrium constant of about 2 is observed between cytochrome f and plastocyanin before 1 ms and after 500 ms after the photochemical reactions. We observe that cytochrome f and plastocyanin are not connected from 1 to 100 ms after a photochemical reaction. The equilibrium constant between plastocyanin and P-700 remains large [20] under these conditions.


Surface Characteristics of Silicon Nanowires/Nanowalls Subjected to Octadecyltrichlorosilane Deposition and n-octadecane Coating.
In this study, nanowires/nanowalls were generated on a silicon wafer through a chemical etching method. Octadecyltrichlorosilane (OTS) was deposited onto the nanowire/nanowall surfaces to alter their hydrophobicity. The hydrophobic characteristics of the surfaces were further modified via a 1.5-μm-thick layer of n-octadecane coating on the OTS-deposited surface. The hydrophobic characteristics of the resulting surfaces were assessed using the sessile water droplet method. Scratch and ultraviolet (UV)-visible reflectivity tests were conducted to measure the friction coefficient and reflectivity of the surfaces. The nanowires formed were normal to the surface and uniformly extended 10.5 μm to the wafer surface. The OTS coating enhanced the hydrophobic state of the surface, and the water contact angle increased from 27° to 165°. The n-octadecane coating formed on the OTS-deposited nanowires/nanowalls altered the hydrophobic state of the surface. This study provides the first demonstration that the surface wetting characteristics change from hydrophobic to hydrophilic after melting of the n-octadecane coating. In addition, this change is reversible; i.e., the hydrophilic surface becomes hydrophobic after the n-octadecane coating solidifies at the surface, and the process again occurs in the opposite direction after the n-octadecane coating melts.


Repair and fixation of potentially lethal damage (PLD) as demonstrated by delayed plating or incubation with araA in contact inhibited refed plateau-phase C3H mouse embryo 10 T1/2 cells grown in the presence of BrdUrd.
C3H mouse 10 T1/2 cells showing strong inhibition of growth at confluency were grown under daily refeeding in the presence of BrdUrd (from 0 to 1 microM) and exposed to gamma-rays either while exponentially growing or in the plateau phase. An increase in radiosensitivity was observed in both growth conditions mainly reflected by a reduction in Dq. Greater radiosensitization was observed in exponentially growing than in plateau-phase cells, and 3-4 times higher BrdUrd concentrations were required in plateau-phase cells for similar potentiation in killing. This effect could not be entirely attributed to a reduction in BrdUrd incorporation since measurements with 3H-BrdUrd showed reductions in incorporation between only 17-47% in plateau-phase cells. The rate of repair of potentially lethal damage (PLD) as demonstrated by delayed plating was not affected by the incorporation of BrdUrd, but the amount of repair (measured as the relative increase in cell survival) was higher for BrdUrd-containing cells. Post-irradiation treatment of cells in the plateau-phase (no BrdUrd) with 9-beta-D-arabinofuranosyladenine (araA) caused fixation of radiation-induced PLD. AraA treatment of cells grown in the presence of various amounts of BrdUrd also caused fixation of PLD, but resulted in survival levels similar to those observed with cells growing in BrdUrd-free medium. This result indicates that BrdUrd mediated radiosensitization cannot be observed when cells are prevented from repairing PLD by postirradiation incubation with araA. Based on these findings we propose that the mechanism of radiosensitization by BrdUrd incorporation might be, by increasing probability of fixation, mediated by the postirradiation progression of cells through the cycle, of a sector of PLD also sensitive to post-irradiation treatment with araA. For this sector of PLD the term alpha-PLD has been proposed.


Development of a serodiagnostic test for sheep scab using recombinant protein Pso o 2.
Early stages of sheep scab, the disease caused by the non-burrowing mite Psoroptes ovis, are often sub-clinical, or can be mis-diagnosed. A diagnostic test capable of detecting early disease and latent infestations is therefore highly desirable in disease control. This paper describes the design and validation of an ELISA, which incorporates a recombinant P. ovis antigen (Pso o 2), for the early detection of anti-P. ovis serum antibodies in sheep. This ELISA was evaluated using sera from sheep infested with P. ovis (n = 58) and sheep (n = 433) with no P. ovis infestation as well as sheep infected with other parasites including gastrointestinal nematodes (GIN), or chewing lice. A receiver operating characteristic (ROC) curve analysis was generated using the ELISA results for 491 sheep sera with the area under the curve (AUC) being 0.97. An optimal OD(450) cut-off of >0.06 absorbance units gave a test sensitivity of 0.93 and specificity of 0.90. The Pso o 2-based ELISA was able to detect specific antibodies to P. ovis during early experimental infestation prior to disease patency, indicating its utility for detecting sub-clinical infestation.


Extra cytoplasmic function σ factor activation.
The bacterial cell envelope is essential for cell viability and is a target for numerous antibiotics and host immune defenses. Thus bacteria must sense and respond to damage to the cell envelope. Many bacteria utilize alternative σ factors such as extracytoplasmic function (ECF) σ factors to respond to cell envelope stress. Although ECF σ factors are utilized by both Gram negative and Gram positive bacteria to respond to cell envelope stress, the mechanisms of sensing differ. In this review, we examine the events and proteins that are required for activation of two model extracytoplasmic function σ factors, σ(E) in E. coli and σ(W) in B. subtilis.


[Hybrid imaging in diagnostics and therapy of chronic myocardial ischemia. Clinical value].
Clinical studies have consistently shown that there is only a very weak correlation between the angiographically determined severity of coronary artery disease (CAD) and disturbance of regional coronary perfusion. On the other hand, the results of randomized trials with a fractional flow reserve (FFR)-guided coronary intervention (DEFER, FAME I, FAME II) showed that it is not the angiographically determined morphological severity of coronary artery disease but the functional severity determined by FFR that is critical for prognosis and the indications for revascularization. A non-invasive method combining the morphological image of the coronary anatomy with functional imaging of myocardial ischemia is therefore particularly desirable. An obvious solution is the combination of coronary computed tomography angiography (CCTA) with a functional procedure, such as perfusion positron emission tomography (PET), perfusion single photon emission computed tomography (SPECT) or perfusion magnetic resonance imaging (MRI). This can be performed with fusion imaging or with hybrid imaging using PET-CT or SPECT-CT. First trial results with PET CCTA and SPECT CCTA carried out as cardiac hybrid imaging on a 64 slice CT showed a major effect to be a decrease in the number of false positive results, significantly increasing the specificity of CCTA and SPECT. Although the results are promising, due to the previously high costs, low availability and the additional radiation exposure, current data is not yet sufficient to give clear recommendations for the use of hybrid imaging in patients with a low to intermediate risk of CAD. Ongoing prospective studies such as the SPARC or EVINCI trials will bring further clarification here.


Taenia saginata cysticercosis in cattle with special reference to its prevalence, pathogenesis and economic implications in Fars Province of Iran.
The study was carried out during a 3-year period. Of 9501 cattle examined, 736 (7.7%) were infected with cysticerci of Taenia saginata. The endemic foci were identified and prevalence was significantly higher (P < 0.005) in animals from Noorabad Mammasani (10.7%), Kenareh (10.0%) and Shiraz area (8.5%) than elsewhere. The prevalence was significantly higher (P < 0.005) during spring and autumn seasons. There was no variation in the infection rate in animals of different age groups, suggesting that immunity was acquired to super-infection. The most common sites were muscle of the shoulder (26.3%) and masseter (23.7%), tongue (24.9%) and heart (23.4%). Pharynx, oesophagus and diaphragm showed 0.9, 0.5 and 0.4% infection, respectively. The metacestode caused extensive damage resulting in infiltrative, degenerative changes, haemorrhages, necrosis and exudation mainly in the vicinity of cysts. The infection was the cause of condemnation of 34.6% of infected carcases. The rejected carcases and infected organs were valued at 100.1 million Rials over the 3-year period.


A novel approach to determine the surface area of buckspoor spider webs and other irregular-shaped two-dimensional objects.
Arising from the practical need to determine the surface area of the buckspoor spider webs of Seothyra schreineri, an approach for area determination was developed based on image processing. The method rendered results that were considered valid and reliable. Aside from the present application to determine the surface area of a spider web, this approach could potentially be used to accurately determine the area of any two-dimensional shape. For each web's photograph:•The boundary of the web was outlined.•Seeded region growing was used to segment the image into a web region and a background region.•The area of the web was determined as a pixel count, and then converted to mm2.


Ionic requirements for the specific binding of [3H]GBR 12783 to a site associated with the dopamine uptake carrier.
At 0 degrees C, when Na+ was the only cation present in the incubation medium, increasing the Na+ concentration from 3 to 10 mM enhanced the affinity of [3H]1-[2-(++di-phenylmethoxy)ethyl]-4-(3-phenyl-2-propenyl)piperaz ine [( 3H]GBR 12783) for the specific binding site present in rat striatal membranes without affecting the Bmax. For higher Na+ concentrations, specific binding values plateaued and then slightly decreased at 130 mM Na+. In a 10 mM Na+ medium, the KD and the Bmax were, respectively, 0.23 nM and 12.9 pmol/mg of protein. In the presence of 0.4 nM [3H]GBR 12783, the half-maximal specific binding occurred at 5 mM Na+. A similar Na+ dependence was observed at 20 degrees C. Scatchard plots indicated that K+, Ca2+, Mg2+, and Tris+ acted like competitive inhibitors of the specific binding of [3H]GBR 12783. The inhibitory potency of various cations (K+, Ca2+, Mg2+, Tris+, Li+, and choline) was enhanced when the Na+ concentration was decreased from 130 to 10 mM. In a 10 mM Na+ medium, the rank order of inhibitory potency was Ca2+ (0.13 mM) greater than Mg2+ greater than Tris+ greater than K+ (15 mM). The requirement for Na+ was rather specific, because none of the other cations acted as a substitute for Na+. No anionic requirement was found: Cl-, Br-, and F- were equipotent. These results suggest that low Na+ concentrations are required for maximal binding; higher Na+ concentrations protect the specific binding site against the inhibitory effect of other cations.


SPECT/CT for sentinel lymph node mapping in head and neck melanoma.
The additional value of single photon emission computed tomography with CT (SPECT/CT) for detection and localization of sentinel nodes in patients with a melanoma of the head and neck was determined. Thirty-eight patients received conventional lymphoscintigraphy followed by hybrid SPECT/CT. The number of sentinel nodes visualized and anatomic information provided were analyzed. Changes in surgical approach due to additional information from the SPECT/CT were evaluated in 20 patients. SPECT/CT visualized a mean of 2.6 sentinel nodes per patient (range, 1-6). SPECT/CT depicted an additional sentinel node in 16% of the patients and clearly showed the anatomic location of the hot nodes in all patients. The surgical approach was adjusted on the basis of SPECT/CT images in 11 patients (55%). SPECT/CT visualizes more sentinel nodes than conventional images and shows their anatomic location. SPECT/CT is recommended in patients with a melanoma in the head or neck.


Comparing bone tissue engineering efficacy of HDPSCs, HBMSCs on 3D biomimetic ABM-P-15 scaffolds in vitro and in vivo.
Human bone marrow mesenchymal stem cells (HBMSCs) has been the gold standard for bone regeneration. However, the low proliferation rate and long doubling time limited its clinical applications. This study aims to compare the bone tissue engineering efficacy of human dental pulp stem cells (HDPSCs) with HBMSCs in 2D, and 3D anorganic bone mineral (ABM) coated with a biomimetic collagen peptide (ABM-P-15) for improving bone-forming speed and efficacy in vitro and in vivo. The multipotential of both HDPSCs and HBMSCs have been compared in vitro. The bone formation of HDPSCs on ABM-P-15 was tested using in vivo model. The osteogenic potential of the cells was confirmed by alkaline phosphatase (ALP) and immunohistological staining for osteogenic markers. Enhanced ALP, collagen, lipid droplet, or glycosaminoglycans production were visible in HDPSCs and HBMSCs after osteogenic, adipogenic and chondrogenic induction. HDPSC showed stronger ALP staining compared to HBMSCs. Confocal images showed more viable HDPSCs on both ABM-P-15 and ABM scaffolds compared to HBMSCs on similar scaffolds. ABM-P-15 enhanced cell attachment/spreading/bridging formation on ABM-P-15 scaffolds and significantly increased quantitative ALP specific activities of the HDPSCs and HBMSCs. After 8 weeks in vivo implantation in diffusion chamber model, the HDPSCs on ABM-P-15 scaffolds showed extensive high organised collagenous matrix formation that was positive for COL-I and OCN compared to ABM alone. In conclusion, the HDPSCs have a higher proliferation rate and better osteogenic capacity, which indicated the potential of combining HDPSCs with ABM-P-15 scaffolds for improving bone regeneration speed and efficacy.


Mechanical and morphological response of confluent epithelial cell layers to reinforcement and dissolution of the F-actin cytoskeleton.
The F-actin cytoskeleton and its connection to the plasma membrane provide structure and shape of epithelial cells. In this study we focus on the impact of the F-actin cytoskeleton on the morphology and mechanical behaviour of confluent epithelial cells. F-actin depolymerisation was fostered by Latrunculin A, while depolymerisation was allayed by Jasplakinolide. The impact of drug treatment on cellular mechanics was measured using atomic force microscopy based active microrheology and force-indentation curves, while morphology was monitored by AFM imaging, electric cell-substrate impedance sensing (ECIS) experiments and fluorescence microscopy. A softening and fluidisation of the cells upon dissolution of F-actin was observed, accompanied by reduction of cell-substrate and cell-cell contacts and an altered topography. The strengthening of actin filaments upon Jasplakinolide treatment was mirrored in several mechanical properties. The largest impact was on the cellular viscosity. The cells were, however, capable of restoring their initial phenotypes, e.g., amount of actin, intercellular and cell-substrate interactions.


Leveraging the neurosurgical operating room for therapeutic development in NeuroOncology.
Glioblastoma (GBM) remains a disease with a dismal prognosis. For all the hope and promise immunotherapies and molecular targeted therapies have shown for systemic malignancies, these treatments have failed to show any promise in GBM. In this context, the paradigm of investigation of therapeutics for this disease itself must be examined and modifications considered. The unique challenge of the presence of blood-brain and blood-tumor barriers (BBB/BTB) raises questions about both the true levels of systemic drug delivery to the affected tissues. Window-of-opportunity (WoO) trials in neuro-oncology allow for proof-of-concept at the start of a classic phase I-II-III clinical trial progression. For therapeutics that do not have the ability to cross the BBB/BTB, direct delivery into tumor and/or tumor-infiltrated brain in the setting of a surgical procedure can provide a novel route of therapeutic access. These approaches permit neurosurgeons to play a greater role in therapeutic development for brain tumors.


Applying A Biopsychosocial Framework to Achieve Durable Behavior Change in Kidney Disease.
Chronic disease self-management is the establishment and maintenance of behaviors needed to be an active participant in one's health care and experience the best health outcomes. Kidney disease self-management behaviors to slow disease progression include engaging in exercise or physical activity; adhering to a diet low in sodium, potassium, and phosphorus; monitoring laboratory parameters; managing complex medication regimens; coping with disease-related emotional distress; and communicating effectively with providers. Durable behavior change has been difficult to achieve in kidney disease, in part because of an incomplete understanding of the multilevel factors determining chronic disease self-management in this patient group. The biopsychosocial model of chronic illness care posits that an individual's health outcomes result from biological, psychological, social, and environmental factors as part of a multilevel systems hierarchy. Although this theoretical model has been used to comprehensively identify factors driving self-management in other chronic conditions, it has been applied infrequently to behavioral interventions in kidney disease. In this scoping review, we apply the biopsychosocial model of health to identify individual, interpersonal, and systems-level drivers of kidney disease self-management behaviors. We further highlight factors that may serve as novel, impactful targets of theory-based behavioral interventions to understand and sustain behavior change in kidney disease.


Acute cerebrovascular insults in homozygous beta-thalassaemia: a case report.
Neurological complications following vascular thrombotic crises are frequent and occur in sickle cell anaemia and its variants, but are less well recognized in thalassaemias. A case of beta-thalassaemia major is reported complicated by an ischaemic lesion involving the right cerebellar hemisphere. The probable pathogenesis is considered and the literature on the matter briefly reviewed. In agreement with other reports, the interference of risk factors provided by or occurring in association with multiple blood-transfusions is hypothesized. Consequently, caution is recommended in giving large blood-transfusions to thalassaemic patients.


Regulation of lipA gene expression by cell surface proteins in arthrobacter photogonimos
Expression of the light-inducible lipA gene in Arthrobacter photogonimos by photodynamic compounds and visible light was inhibited by washing cells with 1 M KCl. Addition of cell surface extract to KCl-washed cells restored the induction. Washing cells with 1 M MgCl2 removed a 14-kDa polypeptide and concomitantly caused expression of lipA gene without photodynamic treatment. The purified 14-kDa polypeptide inhibited photodynamic induction of lipA gene. These results indicated that regulation of lipA gene expression occurred at the cell surface and involved positive and negative factors, probably through a signal transduction system.


A revision of the genus Pontocrates Boeck, 1871 (Amphipoda, Oedicerotidae) with the description of P. moorei sp. nov. and the re-establishment of P. norvegicus (Boeck, 1860).
The genus Pontocrates Boeck, 1871 is revised. Pontocrates norvegicus Boeck (1860), is re-established and a new species, P. moorei sp. nov., is described. An illustrated key to the species of the genus is provided.


Subjective Mouthfeel and Temperature Alterations in COVID-19 Patients Six to Ten Months After Diagnosis.
The characteristics and impact of mouthfeel, temperature, smell, and taste alterations in patients with COVID-19 at a long term are yet not well known. In this study, these characteristics and their impact on daily life and quality of life (QoL) were assessed, six to ten months after infection, in patients with COVID-19 searching for peer support on Facebook. Between December 2020 and January 2021, members of two COVID-19 Facebook groups were invited to complete a questionnaire. Participants were asked to report their perception of mouthfeel, temperature, smell, and taste alterations and their impact. The questionnaire was completed by 157/216 respondents (73%), with 92% being women. Alterations in mouthfeel, temperature, smell, and taste were reported by respectively 66, 40, 148, and 133 participants. The most frequently reported mouthfeel alterations were "a different feeling" and "dry mouth" in 38 and 30 participants, respectively. Preferences for food temperature were equally changed to "freezing", "cool", "room temperature", "a bit warmer", and "warmer". An impact on daily life and QoL was reported by most patients with alterations in mouthfeel (91% and 79%), temperature (78% and 60%), smell (98% and 93%), and taste (93% and 88%), respectively. Patients with COVID-19 searching for peer support on Facebook experienced, next to smell and taste alterations, mouthfeel and temperature disturbances, six to ten months after infection. These alterations have an impact on daily life and QoL. Health professionals should, next to smell and taste alterations, be aware of mouthfeel and temperature alterations in patients with COVID-19. The online version contains supplementary material available at 10.1007/s12078-022-09304-y.


Mobilization practices in critically ill children: a European point prevalence study (EU PARK-PICU).
Early mobilization of adults receiving intensive care improves health outcomes, yet little is known about mobilization practices in paediatric intensive care units (PICUs). We aimed to determine the prevalence of and factors associated with physical rehabilitation in PICUs across Europe. A 2-day, cross-sectional, multicentre point prevalence study was conducted in May and November 2018. The primary outcome was the prevalence of physical therapy (PT)- or occupational therapy (OT)-provided mobility. Clinical data and data on patient mobility, potential mobility safety events, and mobilization barriers were prospectively collected in patients admitted for ≥72 h. Data of 456 children admitted to one of 38 participating PICUs from 15 European countries were collected (456 patient days); 70% were under 3 years of age. The point prevalence of PT- and/or OT-provided mobility activities was 39% (179/456) (95% CI 34.7-43.9%) during the patient days, with significant differences between European regions. Nurses were involved in 72% (924/1283) of the mobility events; in the remaining 28%, PT/OT, physicians, family members, or other professionals were involved. Of the factors studied, family presence was most strongly positively associated with out-of-bed mobilization (aOR 7.83, 95% CI 3.09-19.79). Invasive mechanical ventilation with an endotracheal tube was negatively associated with out-of-bed mobility (aOR 0.28, 95% CI 0.12-0.68). Patients were completely immobile on 25% (115/456) of patient days. Barriers to mobilization were reported on 38% of patient days. The most common reported patient-related barriers were cardiovascular instability (n = 47, 10%), oversedation (n = 39, 9%), and medical contraindication (n = 37, 8%). Potential safety events occurred in 6% of all documented mobilization events. Therapists are infrequently consulted for mobilization of critically ill children in European PICUs. This study highlights the need for a systematic and interdisciplinary mobilization approach for critically ill children.


Total Synthesis of a Partial Structure from Arabinogalactan and Its Application for Allergy Prevention.
Arabinogalactan, a microheterogeneous polysaccharide occurring in plants, is known for its allergy-protective activity, which could potentially be used for preventive allergy treatment. New treatment options are highly desirable, especially in a preventive manner, due to the constant rise of atopic diseases worldwide. The structural origin of the allergy-protective activity of arabinogalactan is, however, still unclear and isolation of the polysaccharide is not feasible for pharmaceutical applications due to a variation of the activity of the natural product and contaminations with endotoxins. Therefore, a pentasaccharide partial structure was selected for total synthesis and subsequently coupled to a carrier protein to form a neoglycoconjugate. The allergy-protective activity of arabinogalactan could be reproduced with the partial structure in subsequent in vivo experiments. This is the first example of a successful simplification of arabinogalactan with a single partial structure while retaining its allergy-preventive potential.


[Mesenchymal stromal cells in the treatment of graft-versus-host disease: where do we stand?].
Medicinal products based on mesenchymal stromal cells (MSC) are expected to have a therapeutic benefit in a variety of conditions and, accordingly, are being tested in many clinical studies. The treatment and prevention of graft-versus-host disease (GVHD) is one of the world's most widely studied MSC therapy concepts. So far, one MSC medicinal product has been approved for the treatment of GvHD. This article gives an overview of the particular features related to the production of MSC-based medicinal products, the state of non-clinical research, and the clinical development status of MSCs and the associated challenges, especially in the context of GvHD.


Open transmetatarsal amputation in the treatment of severe foot infections.
Severe forefoot infections may lead to limb loss, even if addressed aggressively. Infection or gangrene that compromises the plantar skin flap may preclude a standard transmetatarsal or midfoot amputation, thereby culminating in a below-knee amputation. We report a series of forefoot infections with loss of the distal plantar skin. Open or guillotine amputation at the mid-metatarsal level led to a high rate of healing and a durable stump, provided that the level of infection did not extend beyond the metatarsal heads. Wound closure was obtained by wound contracture alone or by use of partial-thickness skin grafting. Rehabilitation was dependable. The association of diabetes mellitus or gangrene did not adversely affect outcome. Open transmetatarsal amputation is a safe surgical option preferable to midfoot or below-knee amputation for the treatment of severe forefoot infection that does not extend proximally beyond the metatarsal heads.


Juvenile systemic lupus erythematosus presenting as pancarditis.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with marked variation in its clinical presentation. Juvenile SLE (jSLE) accounts for 15-20% of all cases and is diagnosed when SLE manifests before 18 years of age. Pancarditis is a rare complication of SLE, regardless of age of disease onset. We report a case of jSLE in a 15 year old Caucasian female presenting with an acute episode of pancarditis and multiorgan dysfunction who was successfully treated with systemic corticosteroids and cyclophosphamide. Pancarditis can be a presenting feature of jSLE which was previously unreported. A high index of suspicion for severe cardiac involvement is required at all stages of disease.


Collagen prolyl 4-hydroxylase is up-regulated in an acute bladder outlet obstruction.
Compliance is primarily related to extracellular matrix deposition, and prolyl 4-hydroxylase (P4Hs) plays a critical role in the synthesis of the matrix. To study the alteration of P4Hs, under the influence of variable hydrostatic pressure, a novel pressure device was used to expose human bladder smooth muscle cells (HBSMC) and fibroblasts (HBF) to pressures in the physiologic range. We then studied acute obstructed porcine bladder tissues to see if changes can also be seen after in-vitro obstruction. HBSMC and HBF were exposed to pressures at 0, 20 and 40 cmH(2)O for up to 72 h. In-vivo studies were carried out next, using six normal (control) and five obstructed porcine bladders. Pigs were exposed to a consistent hydrostatic pressure of < or =20 cm for 24 h after ligation of the urethra. We used 2-DE to compare protein profiling of HBSMC under normal and increased pressures. Other analyses were used to detect molecular alteration and altered expression of mRNA for P4Hs. We identified 437 proteins from 476 spots (91.8%) obtained from HBSMC that were differentially expressed under normal and increased pressures. Under increased pressure, 48 unique proteins were significantly increased or decreased, and a prominent protein regulating extracellular matrix synthesis highly correlated with P4Hs. The exposure of both HBSMC and HBF to a sustained hydrostatic pressure resulted in the increased expression of P4Hs in a time- and pressure-dependent manner. In vivo, P4Hs expression was also significantly increased in the obstructed group. P4Hs is up-regulated, in the human bladder, time and pressure dependently. The alteration of P4Hs over a short period may significantly influence the synthesis of extracellular matrix in vivo and lead to decreased compliance. Our results also support the concept that bladder outlet obstruction, with resultant pressures of 40 cmH(2)O or less, results in molecular changes consistent with decreased compliance.


Human beta-globin mRNAs that harbor a nonsense codon are degraded in murine erythroid tissues to intermediates lacking regions of exon I or exons I and II that have a cap-like structure at the 5' termini.
Previous studies have demonstrated that nonsense codons within beta zero-thalassemic or in vitro-mutagenized human beta-globin transgenes result in the production of mRNAs that are degraded abnormally rapidly in the cytoplasm of murine erythroid cells. As a consequence, three RNA degradative intermediates are formed that lack sequences from either exon I or exons I and II. We show here that the intermediates, like the full-length mRNA from which they derive and the endogenous murine beta maj-globin mRNA, bind to the anticap monoclonal antibody H-20 in a way that is competed by the cap analogue m7G and eliminated by prior exposure to tobacco acid pyrophosphatase. Furthermore, the intermediates, like the two full-length mRNAs, are resistant to a 5'----3' exonuclease activity isolated from HeLa cell nuclei that degrades uncapped but not capped ribopolymers. Based on these observations, the intermediates appear to possess a structure that is indistinguishable from the cap at the 5' end of mRNA, i.e. a methylated nucleoside that is linked to the RNA by a 5'-5' phosphodiester bond. Detection of the intermediates during murine development was concomitant with detection of full-length thalassemic mRNA. Intermediate production appears to be influenced by RNA structure as indicated by the products that derive from a beta zero-thalassemic beta-globin transgene harboring a structural alteration (a 4 bp deletion) that was larger than any of those previously studied.


Effects of psychosocial sleep interventions on improving infant sleep and maternal sleep and mood: A systematic review and meta-analysis.
Infant sleep problems are prevalent and have a negative impact on infant growth and development, maternal sleep, and maternal mood. The effects of psychosocial sleep interventions on infant sleep and maternal sleep and mood are unclear. This study aimed to systematically evaluate the effects of psychosocial sleep interventions on improving infant sleep, including nocturnal total sleep time, daytime total sleep, total sleep time, night wakings, and maternal sleep and mood problems (ie, depression and fatigue). We searched PubMed, Web of Science, Cochrane Library, Embase, EBSCO, OpenGrey, DeepBlue, China National Knowledge Infrastructure, and Wanfang databases. We focused on randomized controlled trials examining the effectiveness of psychosocial sleep interventions on infant sleep. The study was preregistered at the International Prospective Register of Systematic Reviews (CRD42022301654). Thirteen studies from 5889 articles were included in the review, which found that psychosocial sleep interventions improved infant nocturnal total sleep time (0.28 [0.04-0.52], p < 0.05, I2 = 83.9%) and maternal depression (-0.10 [-0.28 to -0.08], p < 0.05, I2 = 8.7%). To test and explore heterogeneity, we used the I2 statistic, influence analysis, subgroup analyses, and subgroup meta-analyses. Funnel plots and Egger's tests revealed no evidence of publication bias. Psychosocial sleep interventions improved infant nocturnal total sleep time and maternal depression. Future research should include more randomized controlled trials examining the effect of psychosocial sleep interventions on the improvement of maternal sleep and fatigue.


Dealing with uncertainty and pursuing superior technology options in risk management--the inherency risk analysis.
Current regulatory systems focus on the state of scientific evidence as the predominant factor for how to handle risks to human health and the environment. However, production and assessment of risk information are costly and time-consuming, and firms have an intrinsic disincentive to produce and distribute information about risks of their products as this could endanger their production opportunities and sales. An emphasis on more or better science may result in insufficient thought and attention going into the exploration of technology alternatives, and that risk management policies miss out on the possible achievement of a more favorable set of consequences. In this article, a method is proposed that combines risk assessment with the search for alternative technological options as a part of the risk management procedure. The method proposed is the inherency risk analysis where the first stage focuses on the original agent subject to investigation, the second stage focuses on identifying technological options whereas the third stage reviews the different alternatives, searching for the most attractive tradeoffs between costs and inherent safety. This is then used as a fundament for deciding which technology option to pursue. This method aims at providing a solution-focused, systematic technology-based approach for addressing and setting priorities for environmental problems. By combining risk assessment with a structured approach to identify superior technology options within a risk management system, the result could very well be a win-win situation for both company and the environment.


Replication initiator DnaA interacts with an anti-terminator NusG in T. tengcongensis.
DnaA plays a central role in initiation of DNA replication at oriC in bacteria, and is also a transcription regulator which interacts with the DnaA box relative to a specific gene. Through screening the interaction between TtDnaA and the transcription machinery in Thermoanaerobacter tengcongensis by yeast two-hybrid assays, we found for the first time that the TtDnaA could interact with an anti-terminator, TtNusG2, in this thermophilic bacterium. The direct interaction between TtDnaA and TtNusG2 was verified by surface plasmon resonance (SPR) assay in vitro, and was further confirmed by co-immunoprecipitation assay in vivo. Moreover, we demonstrated that domain I and domain III of TtDnaA were responsible for the interaction with TtNusG2. These findings might expand our understanding of cooperation of two fundamental processes, replication and transcription, in this bacterium.


Pharmaceutical use among older adults: using administrative data to examine medication-related issues.
Medication use is recognized as the least expensive, most cost-effective health care intervention. In older adults this is especially important, as they are the largest consumer of prescription medications. We describe the use of a linked data set including pharmaceutical, medical, and hospital claims to examine pharmaceutical use in the population of older adults and then give several examples of its application. Indicators to describe the population's overall use of medication and the appropriate use of specific medication have been developed. Indicators of appropriate use are characterized using the dispensation of benzodiazepines to older adults.We have found that a significant proportion of new users of benzodiazepines are still prescribed a long-acting version (over 10%), signifying potential inappropriate use. The data are also able to describe some significant outcomes from the use of pharmaceuticals such a death, fracture, and population-based clinical measures where available.


An organoid-based screen for epigenetic inhibitors that stimulate antigen presentation and potentiate T-cell-mediated cytotoxicity.
In breast cancer, genetic heterogeneity, the lack of actionable targets and immune evasion all contribute to the limited clinical response rates to immune checkpoint blockade therapy. Here, we report a high-throughput screen based on the functional interaction of mouse- or patient-derived breast tumour organoids and tumour-specific cytotoxic T cells for the identification of epigenetic inhibitors that promote antigen presentation and potentiate T-cell-mediated cytotoxicity. We show that the epigenetic inhibitors GSK-LSD1, CUDC-101 and BML-210, identified by the screen, display antitumour activities in orthotopic mammary tumours in mice, that they upregulate antigen presentation mediated by the major histocompatibility complex class I on breast tumour cells and that treatment with BML-210 substantially sensitized breast tumours to the inhibitor of the checkpoint programmed death-1. Standardized measurements of tumour-cell killing activity facilitated by tumour-organoid-T-cell screens may help with the identification of candidate immunotherapeutics for a range of cancers.


[Antidigoxin Fab-fragments in suicidal digoxin poisoning. Successful treatment of recurrent ventricular fibrillation].
A 49-year-old woman took about 12.5 mg digoxin with suicidal intent. Severe arrhythmias, including recurrent ventricular fibrillation, occurred. Sheep Fab fragments of digoxin-specific antibodies were administered i. v. at a dose of 480 mg. Serum free-digoxin concentration fell within half an hour to 0, with simultaneous rise of total digoxin from 13 micrograms/l to a maximum of 176 micrograms/l after 2 hours. At the same time there was marked improvement in the clinical condition with restoration of a stable sinus rhythm. There were no side effects to the Fab fragment administration.


Monosaccharide transport in protein-depleted vesicles from erythrocyte membranes.
Treatment of human erythrocyte membranes with dilute alkali (pH 11.5) generates sealed, protein-depleted vesicles that can be isolated by density gradient centrifugation. The vesicles are 0.5 to 2.0 micrometers in diameter, and their membranes are predominantly oriented inside-out. The vesicles lack protein bands 1, 2, 5, and 6 (nomenclature of Steck, T.L. (1974) J. Cell Biol. 62, 1-19) of the erythrocyte membrane. L-Sorbose, a substrate of the monosaccharide transport system in erythrocytes, is transported by the vesicles. Based on comparisons between erythrocytes and vesicles with regard to specificity, temparture dependence, and effects of inhibitors, we conclude that sorbose uptake into the vesicles occurs by way of the monosaccharide transport system. The specific activity of the transport system in vesicles, as determined by initial rate measurements of sorbose uptake, averaged 58% of that in erythrocytes. This finding indicates that the major polypeptides of Bands 1, 2, 5, and 6 do not play an obligatory role in monosaccharide transport.


A steep decline of death in a shigellosis epidemic in Bangladesh by a community--participated intervention.
The outcome of an intervention of a shigellosis epidemic during April-July 1985 at Dimla, northern Bangladesh is reported. People of the epidemic-affected community operated a makeshift hospital to provide early indoor treatment for 1,708 patients of blood dysentery, based on empirically selected antibiotic(s), oral rehydration of the patients and giving them high-protein diets. They raised funds and received technical and logistic assistance from the physicians and officials of the local government health centre and of the International Centre for Diarrhoeal Disease Research, Bangladesh. In comparison with the number of deaths recorded before intervention, there was a 187-fold reduction of case-fatality ratio from 11.2 to 0.06% (p less than 0.0001). Probable causes for this precipitious decline of mortality are discussed. It is concluded that such a community action in the intervention of a rural shigellosis epidemic in a developing country may avert death almost totally.


[Interactions of 5 benzamides with ethanol on various psychopharmacology tests].
Benzamides interactions with ethanol was studied through five psychopharmacological tests. Ethanol given at 2 or 3 g/kg does not induce potentiation of benzamides effects on: motility, relaxation, dopaminergic effects induced by apomorphine (1 and 16 mg/kg).


Three short postmeal walks as an alternate therapy to continuous walking for women with gestational diabetes.
The purpose of this study was to determine whether postmeal walking (PMW, breaking up exercise into short bouts after meals) is an effective and feasible alternative to continuous walking for the management of gestational diabetes. Forty-one women with gestational diabetes were randomised between weeks 28-30 gestation to either standard care (30 minutes continuous exercise) or standard care with PMW (10 minutes of walking after breakfast, lunch, and dinner). Continuous glucose and activity monitors were worn to measure glycaemic control and adherence during 3 days of standard care (baseline) followed by 3 days of postmeal or continuous walking. A linear mixed model analysed the changes from baseline between postmeal and continuous walking, as an average of the 3-day periods. Thirty-two women (PMW n = 17: control n = 15, 33 ± 5 years, body mass index 25 ± 4 kg·m-2) completed the trial. Postprandial and overnight glucose concentrations were similar between PMW and control; both interventions improved from baseline. There was no difference in adherence between groups; however, PMW completed more minutes of prescribed physical activity across baseline and intervention days compared to the continuous walking standard-care group. Preliminary findings from this proof-of-concept study suggest PMW could be a promising alternative to, and work interchangeably with, traditional advice to perform continuous moderate-intensity physical activity in women with gestational diabetes. Novelty: Three 10-minute postmeal walks may be comparable to 30 minutes continuous walking for glucose control in women with gestational diabetes. Accumulating activity in short bouts after meals is a feasible alternate to continuous exercise for women with gestational diabetes.


Effects of metformin on the bioactivity and osseointegration of dental implants: A systematic review.
Dental implants are prosthetic devices that are surgically placed in direct contact with the jawbone to support intra-oral functions and esthetics. Diabetes mellitus may contribute to peri-implant bone loss. During the last few years, there have been attempts to reduce this bone loss and improve the survival rate of implants. Metformin, an anti-diabetic drug known for its osteogenic properties, is thought to prevent peri-implant bone loss in diabetic patients. Although several studies have been conducted to study metformin's effect on diabetic and non-diabetic study models, no systematic review has analyzed and summarized these studies critically. Therefore, the objectives of this systematic review were to summarize the outcomes of these studies and critically appraise them. Seven studies were included in this systematic review. Four studies used only animal models, two used both animal and cell culture models, and one used only cell culture studies. The general characteristics and outcomes of the included studies were summarized, and Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines were used to assess the quality of the animal studies. In vitro studies indicate that metformin may induce stem cells to undergo osteoblastic differentiation to produce a higher amount of bone and may also improve osseointegration. Nevertheless, several studies had potential sources of bias. Therefore, it is recommended that emphasis be placed on increasing the quality of future animal studies and human trials to determine the effects of metformin on the osseointegration of dental implants. Future studies are needed with adequate follow-up to evaluate the efficacy of metformin in improving the osseointegration of dental implants.


ASB16-AS1 up-regulated and phosphorylated TRIM37 to activate NF-κB pathway and promote proliferation, stemness, and cisplatin resistance of gastric cancer.
Long non-coding RNA (lncRNA) ASB16 antisense RNA 1 (ASB16-AS1) is recognized as an oncogene in several cancer types, but its relation to GC is unknown. Tripartite motif containing 37 (TRIM37) has been proven to accelerate the development of gastric cancer (GC), whereas the molecular mechanism assisted ASB16-AS1 and TRIM37 in regulating GC progression remains unclear. Differentially expressed lncRNAs in GC samples were analyzed based on Gene Expression Omnibus (GEO) data. CCK-8 and colony formation assays were applied to determine the proliferative ability of GC cells. Stem cell-like phenotype of GC cells was assessed by sphere formation assay and flow cytometry analysis. Luciferase reporter assay, RNA immunoprecipitation (RIP), pulldown, and co-immunoprecipitation (Co-IP) were performed to verify the interplay of RNA molecules. ASB16-AS1 was upregulated in GC samples according to GEO data and qRT-PCR analysis. ASB16-AS1 strengthened the proliferative ability and stem cell-like characteristics in GC cells. More importantly, ASB16-AS1 encouraged GC cell growth in vivo. Mechanistically, ASB16-AS1 strengthened TRIM37 expression by sequestering miR-3918 and miR-4676-3p. ASB16-AS1 activated NF-kappa B (NF-κB) pathway by cooperating with ATM serine/threonine kinase (ATM) to induce TRIM37 phosphorylation. In summary, ASB16-AS1 exerted oncogenic functions in GC through modulating TRIM37 expression at both mRNA and protein levels.


Immunohistochemical and molecular detection of the expression of FGF23 in phosphaturic mesenchymal tumors including the non-phosphaturic variant.
Phosphaturic mesenchymal tumors (PMTs) are rare neoplasms that are often associated with tumor-induced osteomalacia (TIO) due to excessive serum levels of fibroblast growth factor 23 (FGF23). PMTs share overlapping histologic features with other types of tumors; thus, accurate pathological diagnosis may be challenging. We performed an immunohistochemical examination of FGF23 expression in PMTs and other types of tumors, together with pertinent molecular analyses. Seven PMTs (5 with TIO and 2 without TIO) and 46 other types of bone and soft tissue tumors were retrieved, and immunohistochemistry was performed using a commercially available anti-FGF23 antibody. In addition, FGF23 mRNA expression was detected by reverse transcription-polymerase chain reaction (RT-PCR), using RNA extracted from formalin-fixed, paraffin-embedded tissues. Immunohistochemical analysis of FGF23 expression showed distinct, punctate staining in the cytoplasm in 5 PMTs with TIO, whereas FGF23 expression was negative in the 2 PMTs without TIO and the other 46 tumors. FGF23 mRNA expression was detected in all 4 PMTs examined, as well as in 1 chondromyxoid fibroma and 1 myxoid liposarcoma. The real-time RT-PCR data showed that the relative expression levels of the FGF23 mRNA tended to be higher in PMTs with TIO than in PMTs without TIO, or in the chondromyxoid fibroma specimen. Our data suggested that the feasibility of immunohistochemical detection of FGF23 may depend on the level of secreted FGF23 from tumor cells. Thus, immunohistochemistry for FGF23 is an useful diagnostic adjunct for PMT, although its utility appears to be limited in cases without TIO.


Anticomplementary activity of stilbenes from medicinal plants.
The anticomplementary activity of stilbenes from medicinal plants in Korea was investigated in vitro. 3,5-Dihydroxy-4'-methoxystilbene (3) was most potent with IC50 value of 1.5 x 10(-4) M followed by rhapontigenin (4), oxyresverastrol (2), 2,3,4',5-tetrahydroxystilbene-2-O-beta-glucoside (9), rhaponticin (8), resverastrol (1), and piceid (7). The activity was found to be increased by a methylation on a hydroxy group of C-4' of 1, but decreased by further methylation on hydroxy groups of C-3 and C-5 and glucosylation on any hydroxy group of 1. Addition of hydroxy group on C-2' of 1 or C-3' of 3 was little affected on the anticomplementary activity but the activity was increased by O-glucosylation on C-2 of 1.


Calcium ion uptake, somatotropin release, and fine structure of somatotrophs in cultures of the rat anterior pituitary upon the action of an oligopeptide (Boc-Gln-Leu-Lysinal).
Cultured cells from the anterior pituitary glands of adult rats were treated with the tripeptide aldehyde proteinase inhibitor, Boc-Gln-Leu-Lys-H. The oligopeptide had a profound releasing effect on growth hormone, whereas the prolactin release remained unchanged at 10(-3) mol/l drug concentration after an incubation for 2 h. In the presence of the oligopeptide a time- and dose-dependent calcium influx into cultured cells has been shown which was proved to be almost completely antagonized with magnesium ions but not with Nifedipine. In addition, radioactive calcium ions could be detected in a number of cells by light microscopic autoradiography when cultures were treated with Boc-Gln-Leu-Lys-H for short periods. The selective Gel action of the oligopeptide on growth hormone producing cells has been demonstrated also in fine structural investigations: multigranular and single exocytotic profiles have been observed. Accordingly, we have postulated that Boc-Gln-Leu-Lysinal mimics the effects of the known ionophores. Its mode of action needs, however, further studies especially on isolated somatotrophs.


Determination of the structural requirements for the inhibitory action of gastrin-releasing peptide on growth hormone release.
We have previously determined that gastrin-releasing peptide (GRP) suppresses plasma growth hormone (GH) levels and blocks the response to growth hormone releasing factor (GRF) following its injection into the third ventricle (3V) of conscious male rats. To determine the portion of the peptide required for this action, fragments of the peptide were injected at various doses to determine their effect on plasma growth hormone and the response to a test dose of GRF (1 microgram/kg IV). The GRP 1-16 lowered plasma GH and blocked the response to GRF following an intraventricular injection of 2 micrograms but not 0.2 microgram of the peptide. Carboxy-terminal fragments were more effective. AcGRP20-27 was partially effective at a 100 times lower dose of 2.0 ng, a result similar to that obtained with the related peptide, bombesin. Even the C-terminal heptapeptide AcGRP-27 was effective at a dose of 2 ng. The results indicate that the C-terminal heptapeptide is the minimal requirement for intraventricularly injected GRP to suppress plasma GH levels and block the response to GRF.


Nasal carbon dioxide for the symptomatic treatment of perennial allergic rhinitis.
Brief nasal carbon dioxide insufflation has previously been shown to provide rapid relief of the symptoms of allergic rhinitis. To examine the safety and efficacy of nasal carbon dioxide on the symptoms of perennial allergic rhinitis. This was a randomized, double-blind, placebo-controlled, multicenter, in-clinic study that evaluated 2 flow rates (5 or 10 mL/s) and 2 administration durations (10 or 30 seconds per nostril) for nasal carbon dioxide vs placebo. Study participants rated their symptoms in clinic for 4 hours after administration and then through 24 hours outside the clinic. A total of 348 symptomatic patients with a minimum 2-year history of perennial allergic rhinitis requiring pharmacotherapy were randomized and treated. The mean change in total nasal symptom score from baseline at 30 minutes (the primary end point) showed greater improvement in the nasal carbon dioxide-treated groups compared with placebo. This change was statistically significant in the group treated with 10 mL/s for 10 seconds per nostril: -4.69 carbon dioxide vs -2.00 placebo (P = .03). The effect of a single dose lasted approximately 4 to 6 hours. The mean change from baseline at 30 minutes in total nonnasal symptom score was also statistically significant (-4.06 carbon dioxide vs -2.25 placebo, P = .029) for this group. The most common adverse events were nasal discomfort, lacrimation, and headache. The study provides further evidence that nasal carbon dioxide is a potentially efficacious treatment for the symptoms of allergic rhinitis.


First description of the male and redescription of the immature stages of Amblyomma rotundatum (Acari: Ixodidae), a recently discovered tick in the U.S.A.
The male of Amblyomma rotundatum is described for the first time, and the nymph and larva are redescribed. This tick is a parthenogenetically reproducing species parasitic on amphibians and reptiles in the warmer areas of the New World. Attempts to mate male and female A. rotundatum under laboratory conditions were unsuccessful.


Epitope mapping of monoclonal antibodies by mass spectrometry: identification of protein antigens in complex biological systems.
We describe the application of immunoaffinity extraction and mass spectrometry to the analysis of Ty1 Gag protein in lysates of Saccharomyces cerevisiae. A magnetic bead-conjugated monoclonal antibody was used to achieve selective extraction, the specificity of which was established by matrix-assisted laser desorption/ionization mass spectrometric (MS) analysis of an extract of the lysate of cells overexpressing the Ty1 Gag protein. MS analysis of similar extracts of lysates following tryptic hydrolysis confirmed selective extraction of the epitope-containing peptide fragment. Sufficient sensitivity was achieved to allow the application of this approach to the analysis of lysates of wild-type cells. Furthermore, the sequence of the epitope-containing peptide was confirmed by electrospray-tandem MS. To our knowledge, this constitutes the first report of the application of immunoaffinity extraction and tandem MS analysis to the characterization of an antigen recovered from a complex cellular system.


Identification and characterization of limbal stem cells.
The maintenance of a healthy corneal epithelium under both normal and wound healing conditions is achieved by a population of stem cells (SC) located in the basal epithelium at the corneoscleral limbus. In the light of the development of strategies for reconstruction of the ocular surface in patients with limbal stem cell deficiency, a major challenge in corneal SC biology remains the ability to identify stem cells in situ and in vitro. Until recently, the identification of limbal stem cells mainly has been based on general properties of stem cells, e.g. lack of differentiation, prolonged label-retaining, indefinite capacity of proliferation exemplified by the clonogenic assay as well as their special role in corneal wound healing. During the last years, a number of molecular markers for the limbal SC compartment has been proposed, however, their role in distinguishing limbal SC from their early progeny is still under debate. Data reported from the literature combined with our own recent observations suggest, that the basal epithelial cells of the human limbus contain ABCG2, K19, vimentin, KGF-R, metallothionein, and integrin alpha9, but do not stain for K3/K12, Cx43, involucrin, P-cadherin, integrins alpha2, alpha6, and beta4, and nestin, when compared to the basal cells of the corneal epithelium. A relatively higher expression level in basal limbal cells was observed for p63, alpha-enolase, K5/14, and HGF-R, whereas there were no significant differences in staining intensity for beta-catenin, integrins alphav, beta1, beta2, and beta5, CD71, EGF-R, TGF-beta-RI, TGF-beta-RII, and TrkA between limbal and corneal basal epithelial cells. Therefore, a combination of differentiation-associated markers (e.g. K3/K12, Cx43, or involucrin) and putative SC-associated markers (e.g. ABCG2, K19, vimentin, or integrin alpha9) may provide a suitable tool for identification of human limbal SC. While most putative SC markers label the majority of limbal basal cells and, therefore, may not distinguish SC from progenitor cells, only ABCG2 was strictly confined to small clusters of basal cells in the limbal epithelium. At present, ABCG2 therefore appears to be the most useful cell surface marker for the identification and isolation of corneal epithelial SC. Moreover, the characteristics of the specific microenvironment of corneal SC, as provided by growth factor activity and basement membrane heterogeneity in the limbal area, could serve as additional tools for their selective enrichment and in vitro expansion for the purpose of ocular surface reconstruction.


Moderating effects of crocin on some stress oxidative markers in rat brain following demyelination with ethidium bromide.
The purpose of this study was to investigate the effects of Crocin on oxidative markers (GPx, SOD, MDA) in animal model of demyelination with Ethidium bromide (EB). Female Wistar rats were assigned in to 4 groups; Sham, with no receiving any agent (Sham), Sham Operated group with injection of EB into the brain received no agent (SO), Sham Treatment group with injection of EB and receiving PBS as vehicle and Treatment group with injection of EB and receiving Crocin (100 mg/kg). Demyelination was induced by single dose injection of 10 μl of EB 0.1% into the Cisterna magna of the brain. Crocin was diluted and applied to each animal for 21 days, once per day gavage. The levels of oxidative markers (GPx, SOD and MDA) were measured by related standard kits. Data were analyzed by paired t-test and ANOVA with post hoc test. The results showed that crocin decreases the levels of GPx and SOD significantly as well as MDA level after 21 days (α ≤ 0.05). In addition, results showed that there were significant differences in the GPx, SOD and MDA levels between all groups at post treatment phase (α ≤ 0.05). It can be concluded that crocin can moderate the level of oxidative markers after demyelination of the brain cells in MS cases. Due to this effect, crocin can be considered as an effective anti-oxidant in management of degenerative nervous system diseases.


Considerations for COVID-19 management in reception centers for refugees, asylum seekers, and migrants, Spain 2020.
Shortly after the declaration of the COVID-19 pandemic, governments around the world were urged to leave no population behind. Following a COVID-19 risk evaluation in a refugee and asylum seekers reception center, in September 2020, we considered the priorities of managing COVID-19 in these settings. We encourage actions on the following four fronts to reduce the COVID-19-associated burden among these vulnerable populations based on our interviews, observations, and recommendations: (i) decongestion, (ii) facilitated testing, (iii) screening for symptoms, and (iv) targeted public health and risk communication.


Acid-active neuraminidases in the growth media from cultures of pathogenic Naegleria fowleri and in sonicates of rabbit alveolar macrophages.
Using bovine mucin and isolated human myelin as sources of sialic acid, we demonstrate the presence of neuraminidase activities in the growth media of pathogenic, but not nonpathogenic, Naegleria sp. and in sonicates of rabbit alveolar macrophages. Neuraminidase activity was maximal at pH 4.5 and 5.0, and the specific activity for sialic acid release was up to 13-fold greater with mucin than with human myelin. Activity in the growth media from cultures of pathogenic Naegleria fowleri was ion-independent, while that of macrophage sonicates required divalent cation; optimal activity was noted with 2.5 mM Zn2+, while Mg2+ and Mn2+ supported activity to a lesser extent. Such acid-active neuraminidases may contribute to the reported glycolipid alterations associated with demyelinating diseases.


Protection against brucellosis in goats, five years after vaccination with reduced-dose Brucella melitensis Rev 1 vaccine.
The protection conferred by the reduced-dose Rev 1 Brucella melitensis vaccine in goats that had been immunized 5 years previously was evaluated. Sixteen goats vaccinated 5 years before with Rev 1 (1 x 10(5) cfu) and 5 non-vaccinated goats were challenged with B. melitensis 16M (4 x 10(5) cfu) using the conjunctival route. After giving birth or aborting, the goats were sacrificed and tissue samples were taken for bacteriological study. The challenge strain was recovered in 12%, of the animals from the vaccinated group, and in (80% of the control group. It is concluded, therefore that the use of reduced-dose Rev 1 protects goats vaccinated in endemic areas for at least 5 years after immunization.


Structural insight into the binding motifs for the calcium ion and the non-catalytic zinc in matrix metalloproteases.
The binding motifs for the structural zinc and calcium ions in matrix metalloproteases (MMPs) were investigated by analyzing the three-dimensional structural models of 23 representative MMPs.


A nucleotide switch in the Escherichia coli DnaA protein initiates chromosomal replication: evidnece from a mutant DnaA protein defective in regulatory ATP hydrolysis in vitro and in vivo.
The ATP-bound DnaA protein opens duplex DNA at the Escherichia coli origin of replication, leading to a series of initiation reactions in vitro. When loaded on DNA, the DNA polymerase III sliding clamp stimulates hydrolysis of DnaA-bound ATP in the presence of the IdaB/Hda protein, thereby yielding ADP-DnaA, which is inactive for initiation in vitro. This negative feedback regulation of DnaA activity is proposed to play a crucial role in the replication cycle. We here report that the mutant protein DnaA R334A is inert to hydrolysis of bound ATP, although its affinities for ATP and ADP remain unaffected. The ATP-bound DnaA R334A protein, but not the ADP form, initiates minichromosomal replication in vitro at a level similar to that seen for wild-type DnaA. When expressed at moderate levels in vivo, DnaA R334A is predominantly in the ATP-bound form, unlike the wild-type and DnaA E204Q proteins, which in vitro hydrolyze ATP in a sliding clamp- and IdaB/Hda-dependent manner. Furthermore, DnaA R334A, but not the wild-type or the DnaA E204Q proteins, promotes overinitiation of chromosomal replication. These in vivo data support a crucial role for bound nucleotides in regulating the activity of DnaA during replication. Based on a homology modeling analysis, we suggest that the Arg-334 residue closely interacts with bound nucleotides.


Correlation between the main clinical, imaging, and arthroscopy findings in patients with temporomandibular disorders.
The purpose of this work was to prospectively correlate the most characteristic clinical symptoms of temporomandibular disorders, such as pain and limitation of mouth opening, with the findings of magnetic resonance imaging (disc position, degenerative changes, and effusion) and arthroscopy findings (roofing, synovitis, chondromalacia, adhesions, and perforations). These examinations were performed in 298 patients diagnosed with internal derangement refractory to conservative treatment. The mean age of the patients was 38.59 years; 92.6% were female. The t-test and one-way analysis of variance (ANOVA) were used to correlate the findings. Significant relationships were found between pain and disc displacement without reduction (P = 0.033) and effusion (P = 0.003) on MRI, coinciding with correlations between pain and roofing of 0-25% (P = 0.016) and synovitis (P = 0.001) on arthroscopy. A significant relationship was also observed between mouth opening limitation and the presence of osteoarthrosis (P = 0.018) on MRI, and between mouth opening limitation and synovitis (P = 0.022), chondromalacia (P = 0.002), and adhesions (P < 0.001) on arthroscopy. All of these findings were observed in patients with a poor initial clinical situation, which highlights the considerable potential of correlating these data with imaging and arthroscopy findings.


Prothrombin G20210A mutation in cases with recurrent miscarriage: a study of the mediterranean population.
Thrombophilic predisposition may be one of the underlying causes of recurrent miscariage (RM). The purpose of this study was to evaluate the Prothrombin G20210A mutation in cases with history of RM. A total of 104 cases, 55 with diagnosis of RM and 49 control cases, were included in this controlled study. In all cases, in addition to full examination tests, Prothrombin 20210A mutation analysis was carried out by means of Polymerase Chain Reaction (PCR). Mean number of the abortion was 3.51 +/- 0.74 in the RM group and 0.08 +/- 0.27 in the control group (p < 0.05). As a consequence of comprehensive examinations, in 24 (43.6%) of 55 RM cases at least one etiologic factor was put forth. Prothrombin G20210A mutation was observed in six (10.9%) cases of the RM group and one (2.04%) in the control group (p < 0.05). Four of the six cases (66.7%) of Prothrombin G20210A mutation had a subsequent pregnancy. Among these four pregnancies, there was one spontaneous loss at 14 weeks of gestation and one severe pre-eclampsia. Our data together with literature suggest that Prothrombin G20210A mutation may be associated with RM. We recommend this genetic testing as a screening tool for women with history of RM.


Successful treatment of refractory type 1 autoimmune hepatitis with methotrexate.
Autoimmune hepatitis is a heterogeneous disorder that typically responds to glucocorticoids with or without azathioprine. Treatment options for patients not responding to standard therapy are limited. We describe a 52-year-old female who presented with jaundice, marked elevation in liver enzymes, positive antinuclear antibody and a liver biopsy consistent with autoimmune hepatitis. Liver enzymes did not normalize with prednisone alone. When azathioprine was added, the disease flared. The patient refused cyclosporine. Methotrexate 7.5 mg po per week resulted in normalization of liver enzymes, improved liver histology, and has maintained remission with a steroid-sparing effect. In this patient methotrexate was used successfully to treat type 1 autoimmune hepatitis. This suggests that methotrexate may have a role in treatment of autoimmune hepatitis refractory to standard therapy.


A modern approach to management of pregnant diabetics: a two-year analysis of perinatal outcomes.
Increased understanding of maternal-fetal carbohydrate homeostasis together with modern perinatal technology now provides a more rational basis for obstetric management of the pregnant diabetic patient. These concepts were applied at MacDonald House in the care of 96 diabetic pregnant women over a two-year period. Pregnancy outcomes were compared with prior experiences with the same group of women. The perinatal mortality rate was reduced from 13.5 to 4.2%, and the rate of macrosomia (infants large for gestational age) was reduced from 30.9 to 17.7%. Patients with gestational diabetes, with a prior loss rate of 8.3%, suffered no losses in the current series. Maternal age was not found to correlate with an untoward outcome in this subgroup.


Evolution and genetic architecture of disassortative mating at a locus under heterozygote advantage.
The evolution of mate choice is a major topic in evolutionary biology because it is thought to be a key factor in trait and species diversification. Here, we aim at uncovering the ecological conditions and genetic architecture enabling the puzzling evolution of disassortative mating based on adaptive traits. This rare form of mate choice is observed for some polymorphic traits but theoretical predictions on the emergence and persistence of this behavior are largely lacking. Thus, we developed a mathematical model to specifically understand the evolution of disassortative mating based on mimetic color pattern in the polymorphic butterfly Heliconius numata. We confirm that heterozygote advantage favors the evolution of disassortative mating and show that disassortative mating is more likely to emerge if at least one allele at the trait locus is free from any recessive deleterious mutations. We modeled different possible genetic architectures underlying mate choice behavior, such as self-referencing alleles, or specific preference or rejection alleles. Our results showed that self-referencing or rejection alleles linked to the color pattern locus enable the emergence of disassortative mating. However, rejection alleles allow the emergence of disassortative mating only when the color pattern and preference loci are tightly linked.


Childhood disintegrative disorder: results of the DSM-IV autism field trial.
This report is concerned with the classification of children in whom an "autistic-like" syndrome develops after some years of normal development. In DSM-IV the term "childhood disintegrative disorder" (CDD) is used to describe such cases. Data collected as part of the international, multisite DSM-IV field trial for autism and related conditions were examined and cases that met DSM-IV criteria for CDD were identified. In 16 cases the clinician had given a CDD diagnosis; in an additional 10 cases criteria for the condition were met even though this diagnosis was not given by the clinician rating the case. The available data suggest that CDD cases can be differentiated from those with autism; these two groups appear to differ in important ways. The identification of cases of CDD may be of particular importance for research.


A mononuclear non-heme high-spin iron(III)-hydroperoxo complex as an active oxidant in sulfoxidation reactions.
We report the first direct experimental evidence showing that a high-spin iron(III)-hydroperoxo complex bearing an N-methylated cyclam ligand can oxidize thioanisoles. DFT calculations showed that the reaction pathway involves heterolytic O-O bond cleavage and that the choice of the heterolytic pathway versus the homolytic pathway is dependent on the spin state and the number of electrons in the d(xz) orbital of the Fe(III)-OOH species.


Early repolarization is an independent predictor of occurrences of ventricular fibrillation in the very early phase of acute myocardial infarction.
Recent evidence has linked early repolarization (ER) to idiopathic ventricular fibrillation (VF) in patients without structural heart disease. However, no studies have clarified whether or not there is an association between ER and the VF occurrences after the onset of an acute myocardial infarction (AMI). This study retrospectively included 220 consecutive patients with an AMI (57 female; mean age, 69±11 years) in whom the 12-lead ECGs before the AMI onset could be evaluated. The patients were classified on the basis of a VF occurrence within 48 hours after the AMI onset. Early repolarization was defined as an elevation of the QRS-ST junction of >0.1 mV from baseline in at least 2 inferior or lateral leads, manifested as QRS slurring or notching. Twenty-one (10%) patients had a VF occurrence within 48 hours of the AMI onset. A multivariate analysis revealed that ER (odds ratio [OR], 7.31; 95% confidence interval [CI], 2.21-24.14; P<0.01), a time from the onset to admission of <180 minutes (OR, 3.77; 95% CI, 1.13-12.59; P<0.05), and a Killip class greater than I (OR, 13.60; 95% CI, 3.43-53.99; P<0.001) were independent predictors of VF occurrences. As features of the ER pattern, a J-point elevation in the inferior leads, greater magnitude of the J-point elevation, notched morphology of the ER, and ER with a horizontal/descending ST segment, all were significantly associated with a VF occurrence. The presence of ER increased the risk of VF occurrences within 48 hours after the AMI onset.


Radiomic analysis of liver grafts from brain-dead donors can predict early allograft dysfunction following transplantation: a proof-of-concept study.
Selection of liver grafts suitable for transplantation (LT) mainly depends on a surgeon's subjective assessment. This study aimed to investigate the role of radiomic analysis of donor-liver CTs after brain death (DBD) to predict the occurrence of early posttransplant allograft dysfunction (EAD). We retrospectively extracted and analyzed the left lobe radiomic features from CT scans of DBD livers in training and validation cohorts. Multivariate analysis was performed to identify predictors of EAD. From 126 LTs included in the study in the training cohort, 27 (21.4%) had an EAD. For each patient, 279 radiomic features were extracted of which 5 were associated with EAD (AUC = 0.81) (95% CI 0.72-0.89). Among donor and recipient clinical characteristics, cardiac arrest, steatosis on donor's CT, cold ischemic time and age of recipient were also identified as independent risk factors for EAD. Combined radiomic signature and clinical risk factors showed a strong predictive performance for EAD with a C-index of 0.90 (95% CI 0.84-0.96). A validation cohort of 23 patients confirmed these results. Radiomic signatures extracted from donor CT scan, independently or combined with clinical risk factors is an objective and accurate biomarker for prediction of EAD after LT.


Hyperventilation and inhibitory synapses.
Injection of a subconvulsive dose of strychnine (which blocked the inhibitory synapses) increases respiratory muscle activity evoked by stimulation of a sciatic nerve as well as by inhalation of hypercapnic gas mixture. Thus the inhibitory synapses prevent an excessive hyperventilation.


The functional effects of Piezo channels in mesenchymal stem cells.
Mesenchymal stem cells (MSCs) are widely used in cell therapy, tissue engineering, and regenerative medicine because of their self-renewal, pluripotency, and immunomodulatory properties. The microenvironment in which MSCs are located significantly affects their physiological functions. The microenvironment directly or indirectly affects cell behavior through biophysical, biochemical, or other means. Among them, the mechanical signals provided to MSCs by the microenvironment have a particularly pronounced effect on their physiological functions and can affect osteogenic differentiation, chondrogenic differentiation, and senescence in MSCs. Mechanosensitive ion channels such as Piezo1 and Piezo2 are important in transducing mechanical signals, and these channels are widely distributed in sites such as skin, bladder, kidney, lung, sensory neurons, and dorsal root ganglia. Although there have been numerous studies on Piezo channels in MSCs in recent years, the function of Piezo channels in MSCs is still not well understood, and there has been no summary of their relationship to illustrate which physiological functions of MSCs are affected by Piezo channels and the possible underlying mechanisms. Therefore, based on the members, structures, and functions of Piezo ion channels and the fundamental information of MSCs, this paper focused on summarizing the advances in Piezo channels in MSCs from various tissue sources to provide new ideas for future research and practical applications of Piezo channels and MSCs.


What predicts employer discrimination? The role of implicit and explicit racial attitudes.
Hiring discrimination against black jobseekers remains prevalent in the United States. Yet, despite strong evidence about the existence of employer discrimination, we know relatively little about what motivates employers' discriminatory behavior. I draw on an original two-wave study with a sample of white hiring agents to examine whether respondents' explicit (deliberate) and implicit (automatic) racial attitudes predict their evaluations of white and black job applicants. Building on dual-process models of the attitude-behavior relationship, I theorize that the hiring process at many U.S. organizations-characterized by ambiguity, time pressure and distractions, and the legitimacy of emotions as a decision-making tool-encourages decision-making based on implicit rather than explicit cognition. Consistent with this theorization, I find implicit, but not explicit, racial attitudes predict respondents' evaluations of white applicants, and of black applicants relative to white applicants. This suggests hiring agents' behavior reflects implicit biases, rather than deliberate avoidance. The results further highlight the role of pro-white bias, not solely anti-black sentiment, in explaining discrimination: implicit attitudes were associated with bias in favor of white jobseekers, not only with discrimination against black jobseekers relative to white jobseekers. Finally, in open-ended responses, hiring agents explain their racially-motivated evaluations without invoking race, suggesting the ambiguity of the hiring process enables them to justify their behavior as colorblind. Together, these findings illustrate how employers can portray an egalitarian image while engaging in racially-motivated behavior.


Transcriptomics of the depressed and PTSD brain.
Stress is the response of an organism to demands for change, yet excessive or chronic stress contributes to nearly all psychiatric disorders. The advent of high-throughput transcriptomic methods such as single cell RNA sequencing poses new opportunities to understand the neurobiology of stress, yet substantial barriers to understanding stress remain. Stress adaptation is an organismal survival mechanism conserved across all organisms, yet there is an infinity of potential stressful experiences. Unraveling shared and separate transcriptional programs for adapting to stressful experience remains a challenge, despite methodological and analytic advances. Here we review the state of the field focusing on the technologies used to study the transcriptome for the stress neurobiologist, and also attempt to identify central questions about the heterogeneity of stress for those applying transcriptomic approaches. We further explore how postmortem transcriptome studies aided by preclinical animal models are converging on common molecular pathways for adaptation to aversive experience. Finally, we discuss approaches to integrate large genomic datasets with human neuroimaging and other datasets.


Serious consequences of Epstein-Barr virus infection: Hemophagocytic lymphohistocytosis.
Human is the host of the Epstein-Barr virus (EBV) especially in childhood and adolescence. Most of them are asymptomatic infection and self-limiting. However, for those patients who suffer from immune dysfunction, EBV infection will be life-threatening. Epstein-Barr virus-associated hemophagocytic lymphohistocytosis (EBV-HLH) is one of the severe effects. The diagnosis and differential diagnosis of EBV-HLH and other EBV infectious diseases are mentioned in this paper. The molecular biology mechanism and complications of EBV-HLH are equally briefly presented. It also provides a practical method for the genetic diagnosis of such diseases and the differential diagnosis with other human immunodeficiency diseases for medical scientists in routine clinical practice.


Quantitative analysis by digital computer of 99mTc-N-pyridoxyl-5-methyltryptophan (99mTc-PMT) hepatogram in diffuse parenchymal liver diseases.
99mTc-N-pyridoxyl-5-methyltryptophan (99mTc-PMT) hepatograms were analyzed to provide information about the liver and bile duct. Calculations were based on a four compartmental model and included corrections for blood, tissue, hepatic parenchymal and bile backgrounds. The time activity curves for 99mTc-PMT in the cardiac region were described as the sum of two exponential functions, while curves for the hepatic regions were described as the sum of three exponential components. The measured hepatograms were compared with simulations and good agreement between the two curves showed that the compartmental model adequately described the blood and bile activities in vivo. Hepatic excretion rate constants were 0.179 +/- 0.026 in three normal subjects, 0.102 +/- 0.012 in four patients with chronic hepatitis and 0.082 +/- 0.034 in six patients with liver cirrhosis. In the case of diffuse parenchymal liver disease, there were lower rate constants for the excretion from the liver to the bile ducts than in normals, and the relative distribution volumes were also larger than normal. Prior to the development of this compartmental model, no useful kinetic model had been found which could satisfactorily explain the time activity curves. Experience in human studies proves this method to be accurate in determining the rate constants for the hepatobiliary transport of 99mTc-PMT.


Unusual case of myoepithelioma associated with adenoid cystic carcinoma of the parotid gland.
Tumors of the salivary glands comprise less than 3% of all neoplasms of the head and neck, with synchronous parotid tumors of differing histologic types being extremely rare. We present a 71-year-old woman with a myoepithelioma associated with an adenoid cystic carcinoma of the left parotid gland. The 48 previously reported cases of synchronous occurring parotid gland tumors of differing histologic types are reviewed.


Coronary perfusion pressure during external chest compression in pseudo-EMD, comparison of systolic versus diastolic synchronization.
The fraction of cardiac arrest patients presenting with pulseless electrical activity is increasing, and it is likely that many of these patients have pseudo-electromechanical dissociation (P-EMD), a state in which there is residual cardiac contraction without a palpable pulse. The efficacy of cardiopulmonary resuscitation (CPR) with external chest compression synchronized with the P-EMD cardiac systole and diastole has not been fully evaluated. During external chest compression in P-EMD, the coronary perfusion pressure (CPP) will be greater with systolic synchronization compared with diastolic phase synchronization. A porcine model of P-EMD induced by progressive hypoxia with peak aortic pressures targeted to 50 mmHg was used. CPR chest compressions were performed by either load distributing band or vest devices. Paired 10s intervals of systolic and diastolic synchronization were performed randomly during P-EMD, and aortic, right atrial and CPP were compared. Stable P-EMD was achieved in 8 animals, with 2.6±0.5 matched synchronization pairs per animal. Systolic synchronization was association with increases in relaxation phase aortic pressure (41.7±8.9 mmHg vs. 36.9±8.2 mmHg), and coronary perfusion pressure (37.6±11.7 mmHg vs. 30.2±9.6 mmHg). Diastolic synchronization was associated with an increased right atrial pressure (6.7±4.1 mmHg vs. 4.1±5.7 mmHg). During P-EMD, synchronization of external chest compression with residual cardiac systole was associated with higher CPP compared to synchronization with diastole.


Peripheral neuropathy in patients with myotonic dystrophy type 1.
To assess the frequency and type of peripheral neuropathy (PNP) in patients with myotonic dystrophy type 1 (DM1), as well as to identify factors that may be associated with this abnormality. This study comprised 111 adult patients with DM1. Nerve conduction study was performed on sural, peroneal and median nerves of both limbs. PNP was somewhat more frequent in DM1 patients with glucose intolerance and diabetes mellitus (66.7 vs. 33.7%, P = 0.05). In DM1 patients with no glucose intolerance, diabetes mellitus and thyroid dysfunction, the most frequent type of PNP was demyelinating (70.0%) and motor (83.3%). PNP was more frequent in males (45.7 vs. 20.9%, P<0.05). Patients with PNP were older (43.7±7.3 vs. 39.6±9.6 years, P<0.05) and had a longer duration of DM1 compared to those without PNP (18.6±9.9 vs 12.7±8.3 years, P<0.01). DM1 patients with PNP had a higher body mass index) (24.9±5.5 vs. 22.4±4.2 kg/cm2, P<0.05), higher triglycerides (3.1±3.3 vs. 1.8±0.8 mmol/l, P<0.01), total cholesterol (6.2±1.4 vs. 5.4±1.1 mmol/l) and LDL cholesterol (4.3±1.2 vs. 3.4±1.0, P<0.05). Achilles reflexes were absent in 76.9% patients with PNP and in 51.9% patients without PNP (P<0.05). Patellar reflexes and muscle strength were similar in both groups (P>0.05). PNP was present in one-third of DM1 patients. The most common type was motor and demyelinating PNP. Our results suggest the association between the presence of peripheral nerve impairment in DM1 and male gender, age, duration of disease and certain metabolic parameters.


Maternal Mortality in Low and Middle-Income Countries.
Despite a 38% decrease in global maternal mortality during the last decade, rates remain unacceptably high with greater than 800 maternal deaths occurring each day. There exists significant regional variation among rates and causes of maternal mortality, and the vast majority occurs in low-income and middle-income countries. The leading causes of direct maternal mortality are hemorrhage, hypertensive disorders of pregnancy, sepsis, complications of abortion, and thromboembolism. Eliminating preventable maternal mortality hinges on improving clinical management of these life-threatening obstetric conditions, as well as addressing the complex social and economic barriers that pregnant women face to access quality care.