Early accretion of water and volatile elements to the inner Solar System: evidence from angrites.
Inner Solar System bodies are depleted in volatile elements relative to chondrite meteorites, yet the source(s) and mechanism(s) of volatile-element depletion and/or enrichment are poorly constrained. The timing, mechanisms and quantities of volatile elements present in the early inner Solar System have vast implications for diverse processes, from planetary differentiation to the emergence of life. We report major, trace and volatile-element contents of a glass bead derived from the D'Orbigny angrite, the hydrogen isotopic composition of this glass bead and that of coexisting olivine and silicophosphates, and the 207Pb-206Pb age of the silicophosphates, 4568 ± 20 Ma. We use volatile saturation models to demonstrate that the angrite parent body must have been a major body in the early inner Solar System. We further show via mixing calculations that all inner Solar System bodies accreted volatile elements with carbonaceous chondrite H and N isotope signatures extremely early in Solar System history. Only a small portion (if any) of comets and gaseous nebular H species contributed to the volatile content of the inner Solar System bodies.This article is part of the themed issue 'The origin, history and role of water in the evolution of the inner Solar System'.


Quantitative modeling of stochastic systems in molecular biology by using stochastic Petri nets.
An integrated understanding of molecular and developmental biology must consider the large number of molecular species involved and the low concentrations of many species in vivo. Quantitative stochastic models of molecular interaction networks can be expressed as stochastic Petri nets (SPNs), a mathematical formalism developed in computer science. Existing software can be used to define molecular interaction networks as SPNs and solve such models for the probability distributions of molecular species. This approach allows biologists to focus on the content of models and their interpretation, rather than their implementation. The standardized format of SPNs also facilitates the replication, extension, and transfer of models between researchers. A simple chemical system is presented to demonstrate the link between stochastic models of molecular interactions and SPNs. The approach is illustrated with examples of models of genetic and biochemical phenomena where the ULTRASAN package is used to present results from numerical analysis and the outcome of simulations.


Identification of a functionally important sequence in the cytoplasmic tail of integrin beta 3 by using cell-permeable peptide analogs.
Integrins are major two-way signaling receptors responsible for the attachment of cells to the extracellular matrix and for cell-cell interactions that underlie immune responses, tumor metastasis, and progression of atherosclerosis and thrombosis. We report the structure-function analysis of the cytoplasmic tail of integrin beta 3 (glycoprotein IIla) based on the cellular import of synthetic peptide analogs of this region. Among the four overlapping cell-permeable peptides, only the peptide carrying residues 747-762 of the carboxyl-terminal segment of integrin beta 3 inhibited adhesion of human erythroleukemia (HEL) cells and of human endothelial cells (ECV) 304 to immobilized fibrinogen mediated by integrin beta 3 heterodimers, alpha IIb beta 3, and alpha v beta 3, respectively. Inhibition of adhesion was integrin-specific because the cell-permeable beta 3 peptide (residues 747-762) did not inhibit adhesion of human fibroblasts mediated by integrin beta 1 heterodimers. Conversely, a cell-permeable peptide representing homologous portion of the integrin beta 1 cytoplasmic tail (residues 788-803) inhibited adhesion of human fibroblasts, whereas it was without effect on adhesion of HEL or ECV 304 cells. The cell-permeable integrin beta 3 peptide (residues 747-762) carrying a known loss-of-function mutation (Ser752Pro) responsible for the genetic disorder Glanzmann thrombasthenia Paris I did not inhibit cell adhesion of HEL or ECV 304 cells, whereas the beta 3 peptide carrying a Ser752Ala mutation was inhibitory. Although Ser752 is not essential, Tyr747 and Tyr759 form a functionally active tandem because conservative mutations Tyr747Phe or Tyr759Phe resulted in a nonfunctional cell permeable integrin beta 3 peptide. We propose that the carboxyl-terminal segment of the integrin beta 3 cytoplasmic tail spanning residues 747-762 constitutes a major intracellular cell adhesion regulatory domain (CARD) that modulates the interaction of integrin beta 3-expressing cells with immobilized fibrinogen. Import of cell-permeable peptides carrying this domain results in inhibition "from within" of the adhesive function of these integrins.


[Recombinant human TSH in pediatric thyroid cancer].
The treatment of pediatric thyroid cancer usually includes thyroid surgery, therapeutic radioactive iodine ablation, and TSH suppression with levotiroxine. Thyroid hormone withdrawal in the usual follow-up of thyroid cancer has adverse effects on patients. Recominant human (Rh) TSH has the advantage of avoiding both hypothyroidism, with a major impact on the patient's quality of life, and the side effects on tumor growth related to the long-lasting TSH increase. Rh TSH has proven to be effective and safe, but the majority of publications are based on adult population. In this report we present our experience with the administration of Rh TSH in the diagnostic evaluation for treatment in a series of four cases of thyroid cancer in children. In all cases we observed clinical benefits without secondary effects. In conclusion Rh TSH is an appropriate treatment option for the disease and represents a valuable alternative to thyroxin withdrawal.


Non-optimal levels of dietary selenomethionine alter splenocyte response and modify oxidative stress markers in female mice.
Many studies evaluating the effects of selenium (Se) status on immunity utilize inorganic Se, although selenomethionine (Se-Met) has been suggested to be more bioavailable and less toxic. In the current study, we investigated the effects of dietary Se-Met on immune system function and cellular redox status in C57BL/6N female mice fed with low (0.02 ppm), sufficient (0.2 ppm, control group), or excess Se-Met (2 ppm) in the diet for 50 days. Low Se-Met intake reduced glutathione peroxidase (GPx) activity and glutathione concentration without modifying lipoperoxidation. While low Se-Met intake also reduced the number of B cells in the spleen, it increased mitogen-induced proliferation, IL-4 and IL-12 secretion when compared to the sufficient Se-Met intake group. In comparison to controls, excess Se-Met intake increased splenocyte proliferation and reduced B cell numbers, IL-4, and IL-12 secretion without affecting oxidative stress markers. These data suggest that Se-Met supplementation should be carefully evaluated as it many influence immune function.


Increased expression of CYP4Z1 promotes tumor angiogenesis and growth in human breast cancer.
Cytochrome P450 (CYP) 4Z1, a novel CYP4 family member, is over-expressed in human mammary carcinoma and associated with high-grade tumors and poor prognosis. However, the precise role of CYP4Z1 in tumor progression is unknown. Here, we demonstrate that CYP4Z1 overexpression promotes tumor angiogenesis and growth in breast cancer. Stable expression of CYP4Z1 in T47D and BT-474 human breast cancer cells significantly increased mRNA expression and production of vascular endothelial growth factor (VEGF)-A, and decreased mRNA levels and secretion of tissue inhibitor of metalloproteinase-2 (TIMP-2), without affecting cell proliferation and anchorage-independent cell growth in vitro. Notably, the conditioned medium from CYP4Z1-expressing cells enhanced proliferation, migration and tube formation of human umbilical vein endothelial cells, and promoted angiogenesis in the zebrafish embryo and chorioallantoic membrane of the chick embryo. In addition, there were lower levels of myristic acid and lauric acid, and higher contents of 20-hydroxyeicosatetraenoic acid (20-HETE) in CYP4Z1-expressing T47D cells compared with vector control. CYP4Z1 overexpression significantly increased tumor weight and microvessel density by 2.6-fold and 1.9-fold in human tumor xenograft models, respectively. Moreover, CYP4Z1 transfection increased the phosphorylation of ERK1/2 and PI3K/Akt, while PI3K or ERK inhibitors and siRNA silencing reversed CYP4Z1-mediated changes in VEGF-A and TIMP-2 expression. Conversely, HET0016, an inhibitor of the CYP4 family, potently inhibited the tumor-induced angiogenesis with associated changes in the intracellular levels of myristic acid, lauric acid and 20-HETE. Collectively, these data suggest that increased CYP4Z1 expression promotes tumor angiogenesis and growth in breast cancer partly via PI3K/Akt and ERK1/2 activation.


The role of members of the pertussis toxin-sensitive family of G proteins in coupling receptors to the activation of the G protein-gated inwardly rectifying potassium channel.
Inwardly rectifying potassium (K(+)) channels gated by G proteins (Kir3.x family) are widely distributed in neuronal, atrial, and endocrine tissues and play key roles in generating late inhibitory postsynaptic potentials, slowing the heart rate and modulating hormone release. They are directly activated by G(betagamma) subunits released from G protein heterotrimers of the G(i/o) family upon appropriate receptor stimulation. Here we examine the role of isoforms of pertussis toxin (PTx)-sensitive G protein alpha subunits (G(ialpha1-3) and G(oalphaA)) in mediating coupling between various receptor systems (A(1), alpha(2A), D(2S), M(4), GABA(B)1a+2, and GABA(B)1b+2) and the cloned counterpart of the neuronal channel (Kir3.1+3.2A). The expression of mutant PTx-resistant G(i/oalpha) subunits in PTx-treated HEK293 cells stably expressing Kir3.1+3.2A allows us to selectively investigate that coupling. We find that, for those receptors (A(1), alpha(2A)) known to interact with all isoforms, G(ialpha1-3) and G(oalphaA) can all support a significant degree of coupling to Kir3.1+3.2A. The M(4) receptor appears to preferentially couple to G(ialpha2) while another group of receptors (D(2S), GABA(B)1a+2, GABA(B)1b+2) activates the channel predominantly through G(betagamma) liberated from G(oA) heterotrimers. Interestingly, we have also found a distinct difference in G protein coupling between the two splice variants of GABA(B)1. Our data reveal selective pathways of receptor activation through different G(i/oalpha) isoforms for stimulation of the G protein-gated inwardly rectifying K(+) channel.


Pervasive self-care solutions in telecardiology. Typical use cases from the EPI-MEDICS project.
In western countries, heart disease is the main cause of premature death. Most of cardiac deaths occur out of hospital. Because of a continuously growing elderly population, the number of heart attacks is steadily increasing. Symptoms are often interpreted incorrectly. Victims do not survive long enough to benefit from inhospital treatments. To reduce the time before treatment, the only useful diagnostic tool to assess the presence of a cardiac event is the electrocardiogram (ECG). Event and transtelephonic ECG recorders are used to improve decision-making but require setting up new infrastructures. The pervasive solution proposed by the European EPI-MEDICS project is an intelligent Personal ECG Monitor for the early detection of cardiac events. It includes part of the patient electronic health record (EHR), embeds a web server and decision-making techniques, generates different alarm levels and forwards alarm messages to the relevant care providers by means of new generation wireless communication. It is cost saving, involving care providers only if necessary, without requiring to set-up specific infrastructures. Healthcare becomes personalized, wearable and ubiquitous.


Implementation of crowding solutions from the American College of Emergency Physicians Task Force Report on Boarding.
We sought to measure the self-reported implementation of the crowding solutions outlined in the 2008 American College of Emergency Physicians (ACEP) Boarding Task Force report "Emergency Department Crowding: High-Impact Solutions." We also tested the hypothesis that the self-reported crowding of emergency departments (EDs) was positively associated with the implementation of these solutions. In early 2009, we mailed a survey to all medical or nursing directors from EDs in four US states asking for information regarding their EDs in 2008. Geographic information about the EDs was included in the analysis, along with survey responses about their ED capacity status and implementation of specific ACEP crowding solutions. A total of 284 of 351 EDs responded (81%). The majority of EDs were in urban areas (56%), non-teaching hospitals (93%), and not critical access hospitals (76%). The percentage of EDs "over capacity" ranged from 10-49% in each state. The mean number of crowding solutions used in EDs that were at or over capacity ranged from 3.6-4.6 in each state. EDs with visit volumes greater than or equal to three patients/hour were more likely to be over capacity than at capacity or at a good balance (46% vs. 31% and 15%, respectively). In terms of the use of high-impact crowding solutions, hospitals over capacity were more likely to utilize inpatient full capacity protocols (40% vs. 25% and 25%) but not inpatient discharge coordination (29% vs. 27% and 34%) or surgical schedule smoothing (31% vs. 28% and 32%). Hospitals over capacity were also more likely to have fast track units (44% vs. 32% and 16%) and physicians at triage (48% vs. 29% and 17%). Less than half of EDs in each state reported operation above capacity. Implementation of some crowding solutions was more common in the above-capacity EDs, although these solutions were not consistently used across geographic locations and hospitals. Given that the majority of EDs were not over capacity, the implementation of these solutions does not seem to be universally necessary.


Treatment change comparisons among white adolescents with skeletal Class I and II relationships with 3 different vertical divergencies-part 2: Holdaway difference.
The Holdaway difference represents the relationship of the NB line to the mandibular incisor (NB-L1) and the bony pogonion (NB-Pog). This study aimed to evaluate treatment changes of NB-L1, NB-Pog, and the Holdaway difference in patients with skeletal Class I and II relationships with 3 different skeletal divergencies. This retrospective study was the second part of treatment outcome assessments of 135 white adolescent patients (females, n = 69; males, n = 66; mean age, 12.8 ± 1.4 years pretreatment and 15.0 ± 1.4 years posttreatment). The NB-L1, NB-Pog, and Holdaway differences (NB-L1 - NB-Pog) were measured. The mixed-model analysis of variance was used to assess within- and between-subject effects responding to horizontal and vertical skeletal discrepancies. For the group with favorable profile changes, the means of the Holdaway difference were maintained in the hypodivergent and normodivergent subgroups and reduced in the hyperdivergent subgroups for patients with skeletal Class I and II relationships. The means of NB-L1 and Holdaway difference were significantly larger in the skeletal Class II group and became greater as skeletal vertical divergencies increased. The NB-Pog means were significantly different only between the hypodivergent and hyperdivergent subgroups. Based on the findings of this study, the Holdaway difference should be adjusted to individualize the incisor positions, considering not only the anteroposterior but also the vertical skeletal relationships of the patients.


Automatic radiomic feature extraction using deep learning for angiographic parametric imaging of intracranial aneurysms.
Angiographic parametric imaging (API) is an imaging method that uses digital subtraction angiography (DSA) to characterize contrast media dynamics throughout the vasculature. This requires manual placement of a region of interest over a lesion (eg, an aneurysm sac) by an operator. The purpose of our work was to determine if a convolutional neural network (CNN) was able to identify and segment the intracranial aneurysm (IA) sac in a DSA and extract API radiomic features with minimal errors compared with human user results. Three hundred and fifty angiographic images of IAs were retrospectively collected. The IAs and surrounding vasculature were manually contoured and the masks put to a CNN tasked with semantic segmentation. The CNN segmentations were assessed for accuracy using the Dice similarity coefficient (DSC) and Jaccard index (JI). Area under the receiver operating characteristic curve (AUROC) was computed. API features based on the CNN segmentation were compared with the human user results. The mean JI was 0.823 (95% CI 0.783 to 0.863) for the IA and 0.737 (95% CI 0.682 to 0.792) for the vasculature. The mean DSC was 0.903 (95% CI 0.867 to 0.937) for the IA and 0.849 (95% CI 0.811 to 0.887) for the vasculature. The mean AUROC was 0.791 (95% CI 0.740 to 0.817) for the IA and 0.715 (95% CI 0.678 to 0.733) for the vasculature. All five API features measured inside the predicted masks were within 18% of those measured inside manually contoured masks. CNN segmentation of IAs and surrounding vasculature from DSA images is non-inferior to manual contours of aneurysms and can be used in parametric imaging procedures.


A single class of neurotensin receptors with high affinity in neuroblastoma X glioma NG108-15 hybrid cells that mediate facilitation of synaptic transmission.
Receptor binding of [3H]neurotensin was examined on membrane preparations derived from neuroblastoma X glioma NG108-15 hybrid cells. The specific binding was saturable and reversible, and a dissociation constant (Kd) was calculated to be about 0.24 nM from the rate constants. Scatchard analysis of neurotensin binding at equilibrium revealed a single class of binding sites with a Kd of 0.86 nM and a maximal binding capacity (Bmax) of 250 fmol/mg of protein (7700 receptor sites/cell). [D-Arg9]-Neurotensin had a high affinity (IC50 = 0.5 nM) for the neurotensin receptors, but [D-Phe11]-neurotensin had a lower affinity (IC50 = 280 nM), while angiotensin II and bradykinin had almost no affinity for [3H]neurotensin-binding sites. Under similar conditions [3H]neurotensin binding to mouse and rat brain synaptosomal fractions showed two binding sites with high (0.86 and 0.44 nM) and low (13 and 19 nM) affinities. We have examined several possible physiological consequences of neurotensin receptor binding. Neurotensin (10 microM) exhibited no influence on adenylate cyclase activity, 45Ca uptake, or 32Pi incorporation into phosphatidylinositol fractions of NG108-15 cells. Electrophysiological study of isolated NG108-15 cells revealed neurotensin-induced transient hyperpolarization followed by sustained depolarization with enhanced membrane excitability. Application of neurotensin to NG108-15 cells that had formed synapses with cultured striated muscle cells caused a considerable increase in frequency of miniature endplate potentials from the muscle cells. These data show that NG108-15 cells possess a single class of neurotensin receptors similar to a high affinity site of synaptosomal membranes from the murine brains.(ABSTRACT TRUNCATED AT 250 WORDS)


Humidity and multiscale structure govern mechanical properties and deformation modes in films of native cellulose nanofibrils.
Nanopapers formed by stiff and strong native cellulose nanofibrils are emerging as mechanically robust and sustainable materials to replace high-performance plastics or as flexible, transparent and "green" substrates for organic electronics. The mechanical properties endowed by nanofibrils crucially depend on mastering structure formation processes and on understanding interfibrillar interactions as well as deformation mechanisms in bulk. Herein, we show how different dispersion states of cellulose nanofibrils, that is, unlike tendencies to interfibrillar aggregation, and different relative humidities influence the mechanical properties of nanopapers. The materials undergo a humidity-induced transition from a predominantly linear elastic behavior in dry state to films displaying plastic deformation due to disengagement of the hydrogen-bonded network and lower nanofibrillar friction at high humidity. A concurrent loss of stiffness and tensile strength of 1 order of magnitude is observed, while maximum elongation stays near constant. Scanning electron microscopy imaging in plastic failure demonstrates pull-out of individual nanofibrils and bundles of nanofibrils, as well as larger mesoscopic layers, stemming from structures organized on different length scales. Moreover, multiple yielding phenomena and substantially increased elongation in strongly disengaged networks, swollen in water, show that strain at break in such nanofibril-based materials is coupled to relaxation of structural entities, such as cooperative entanglements and aggregates, which depend on the pathway of material preparation. The results demonstrate the importance of controlling the state of dispersion and aggregation of nanofibrils by mediating their interactions, and highlight the complexity associated with understanding hierarchically structured nanofibrillar networks under deformation.


Polish women labour inspectors between the world wars: scrutinizing the workplace and mobilizing public opinion.
This article explores the history of women's activism within the state apparatus, focusing on women labour inspectors in interwar Poland. Part of the State Labour Inspectorate since its creation in 1919, women inspectors often combined their professional duties with a distinctly activist stance. Like their male colleagues, they ensured compliance with labour legislation by performing factory visits and collecting information on the conditions of workers' lives and labour. But they also led campaigns in the press, published books and brochures intended to mobilize public opinion around issues related to the labour of women and minors, and sought to build activist networks aimed at the improvement of women workers' conditions. They exposed particularly exploitative labour arrangements, such as the labour of underage apprentices, and conceptualized them as urgent social problems. These multiple engagements meant that women labour inspectors moved between different scales of action including direct intervention on the shop floor, research and publications aimed at a national audience, and transnational contacts with the International Labour Organization, which had been committed to improving women workers' conditions since its inception.


Evaluation of hemoglobin A1c criteria to assess preoperative diabetes risk in cardiac surgery patients.
Hemoglobin A1c (A1C) has recently been recommended for diagnosing diabetes mellitus and diabetes risk (prediabetes). Its performance compared with fasting plasma glucose (FPG) and 2-h post-glucose load (2HPG) is not well delineated. We compared the performance of A1C with that of FPG and 2HPG in preoperative cardiac surgery patients. Data from 92 patients without a history of diabetes were analyzed. Patients were classified with diabetes or prediabetes using established cutoffs for FPG, 2HPG, and A1C. Sensitivity and specificity of the new A1C criteria were evaluated. All patients diagnosed with diabetes by A1C also had impaired fasting glucose, impaired glucose tolerance, or diabetes by other criteria. Using FPG as the reference, sensitivity and specificity of A1C for diagnosing diabetes were 50% and 96%, and using 2HPG as the reference they were 25% and 95%. Sensitivity and specificity for identifying prediabetes with FPG as the reference were 51% and 51%, respectively, and with 2HPG were 53% and 51%, respectively. One-third each of patients with prediabetes was identified using FPG, A1C, or both. When testing A1C and FPG concurrently, the sensitivity of diagnosing dysglycemia increased to 93% stipulating one or both tests are abnormal; specificity increased to 100% if both tests were required to be abnormal. In patients before cardiac surgery, A1C criteria identified the largest number of patients with diabetes and prediabetes. For diagnosing prediabetes, A1C and FPG were discordant and characterized different groups of patients, therefore altering the distribution of diabetes risk. Simultaneous measurement of FGP and A1C may be a more sensitive and specific tool for identifying high-risk individuals with diabetes and prediabetes.


Replication of the nonconjugative plasmid RSF1010 in Escherichia coli K-12.
Replicating DNA molecules of the nonconjugative R plasmid RSF1010 (Smr Sur) were cleaved with the EcoRI restriction endonuclease and examined with the electron microscope. Results of this analysis indicated that replication is initiated from an origin located at about 19% of total genome size from one of the EcoRI ends. Replication proceeded either unidirectionally or bidirectionally with equal frequency. Results of the analysis of replicative intermediates of RSF1010 containing the Apr-transposable sequence (Tn) are also presented.


Non-invasive estimated continuous cardiac output (escCO) during severe sepsis and septic shock resuscitation.
Cardiac output (CO) is an important hemodynamic parameter during sepsis and septic shock resuscitation. Conventionally, this value is obtained at bedside by the thermodilution technique, which requires a pulmonary artery catheter (PAC). Estimated Continuous Cardiac Output (esCCO, Nihon Kohden, Japan) calculated from pulse-wave transit time (PWTT) was examined here as an alternative. A prospective study was performed in a 14-bed ICU facility. Patients with severe sepsis and septic shock who had PAC placed were included. Serial thermodilution cardiac outputs (CO(IBT)) and esCCO (COesCCO) were obtained at the beginning of resuscitation (t0), at 48 hours (t48), and at 72 hours (t72). Other parameters from the tested device; namely, estimated continuous cardiac index (esCCI), estimated stroke volume (esSV), and estimated stroke volume index (esSVI), were also achieved. A total of 90-paired readings from ten ICU patients were collected. The overall correlation coefficient (R) between COesCCO and CO(IBT) was 0.76. When focusing on the correlation from each time point, we found R at t0 = 0.65, t48 = 0.74, and t72 = 0.84 (all p < 0.001). Bland and Altman analysis corrected for repeated measures showed a bias of 1.2 liter/min and limits of agreement from -2.8 to +5.2 liter/min. Results also showed fair to poor correlation with other parameters that derived from this device (esCCI, esSV esSVI). The estimated continuous cardiac output (esCCO) correlated well with the cardiac output obtained by thermodilution techniques, especially when patients were out of shock.


Developing a Unifying Model of Resilience in Dementia Caregiving: A Scoping Review and Content Analysis.
Resilience, a capacity for addressing, recovering, and growing from challenging situations, can mitigate dementia care partners' burden. Three main theoretical models predominate, treating resilience variably as an outcome, a trait, or a process. In this scoping review, we examine how these three models inform definitions and measures of resilience in dementia care partners to understand whether there is a single coherent model and identify the gaps in conceptualizing and operationalizing resilience. We searched English-language peer-reviewed articles (January 1991-June 2019) that contained definitions and/or measures of resilience developed for or used with dementia care partners. Data were analyzed using content analysis. We found that perspectives from the three existing theoretical models can be integrated into a unified framework for the study of resilience in dementia care partners. However, major gaps remain in operationalizing resilience for research due to a paucity of resilience outcomes and knowledge about resilience-related behaviors.


Contributions of Traffic and Industrial Emission Reductions to the Air Quality Improvement after the Lockdown of Wuhan and Neighboring Cities Due to COVID-19.
Wuhan was locked down from 23 January to 8 April 2020 to prevent the spread of the novel coronavirus disease 2019 (COVID-19). Both public and private transportation in Wuhan and its neighboring cities in Hubei Province were suspended or restricted, and the manufacturing industry was partially shut down. This study collected and investigated ground monitoring data to prove that the lockdowns of the cities had significant influences on the air quality in Wuhan. The WRF-CMAQ (Weather Research and Forecasting-Community Multiscale Air Quality) model was used to evaluate the emission reduction from transportation and industry sectors and associated air quality impact. The results indicate that the reduction in traffic emission was nearly 100% immediately after the lockdown between 23 January and 8 February and that the industrial emission tended to decrease by about 50% during the same period. The industrial emission further deceased after 9 February. Emission reduction from transportation and that from industry was not simultaneous. The results imply that the shutdown of industry contributed significantly more to the pollutant reduction than the restricted transportation.


Assessment of percutaneous laparoscopic ultrasonography-guided core needle biopsy for the advanced diagnosis of unresectable pancreatic cancer.
Before the initiation of cytotoxic therapy for locally unresectable pancreatic cancer, staging laparoscopy is an important diagnostic method for both the detection of occult small lesions and the extraction of a tumor sample for advanced pathological examination using core needle biopsy (CNB) under laparoscopic ultrasonography (LUS) guidance. This study aimed to evaluate the safety and usefulness of LUS-guided CNB in pancreatic cancer. Consecutive patients with locally unresectable pancreatic cancer who underwent staging laparoscopy were retrospectively analyzed. LUS-guided CNB was performed percutaneously under a laparoscopic view. The clinical results of the LUS-guided CNB group and the non-LUS-guided CNB group were compared. Forty-eight patients who underwent staging laparoscopy by LUS-guided CNB or endoscopic ultrasound-guided fine needle aspiration were identified. LUS-guided CNB was performed in 25 patients. The mean tumor size in the LUS-guided CNB group was significantly larger than that in the non-LUS-guided CNB group. No significant difference was observed between the two groups in operating time or bleeding volume. The rates of malignancy diagnosis and histological classification subtyping were significantly higher in the LUS-guided CNB group. Histologically differentiated adenocarcinoma was identified in 15 patients using samples acquired by LUS-guided CNB. There was no uncontrollable bleeding or other complications, and a significant difference in the occurrence of peritoneal dissemination after laparoscopic examination was observed between the two groups. LUS-guided CNB enables the safe acquisition of sufficient tissue volumes for certain pathological analyses required to determine treatment strategies for locally unresectable advanced pancreatic cancer.


Genistein supplementation increases bone turnover but does not prevent alcohol-induced bone loss in male mice.
Chronic alcohol consumption results in bone loss through increased bone resorption and decreased bone formation. These effects can be reversed by estradiol (E2) supplementation. Soy diets are suggested to have protective effects on bone loss in men and women, as a result of the presence of soy protein-associated phytoestrogens such as genistein (GEN). In this study, male mice were pair-fed (PF), a control diet, an ethanol (EtOH) diet, or EtOH diet supplemented with 250 mg/kg of GEN for 8 weeks to test if GEN protects against bone loss associated with chronic drinking. Interestingly, alcohol consumption reduced cortical area and thickness and trabecular bone volume in both EtOH and EtOH/GEN groups when compared to the corresponding PF and PF/GEN controls, P < 0.05. However, in the trabecular bone compartment, we observed a significant increase in overall trabecular bone density in the PF/GEN group compared to the PF controls. Bone loss in the EtOH-treated mice was associated with the inhibition of osteoblastogenesis as indicated by decreased alkaline phosphatase staining in ex vivo bone marrow cultures, P < 0.05. GEN supplementation improved osteoblastogenesis in the EtOH/GEN cultures compared to the EtOH group, P < 0.05. Vertebral expression of bone-formation markers, osteocalcin, and runt-related transcription factor 2 (Runx2) was also significantly up-regulated in the PF/GEN and EtOH/GEN groups compared to the PF and EtOH-treated groups. GEN supplementation also increased the expression of receptor activator of nuclear factor κ-B ligand (RANKL) in the PF/GEN, an increase that persisted in the EtOH/GEN-treated animals (P < 0.05), and increased basal hydrogen peroxide production and RANKL mRNA expression in primary bone marrow cultures in vitro, P < 0.05. These findings suggest that GEN supplementation increases the overall bone remodeling and, in the context of chronic alcohol consumption, does not protect against the oxidative stress-associated EtOH-mediated bone resorption.


Most patients with arterial hypertension (AH) for successful long-term blood pressure (BP) control require combination of antihypertensive drugs acting on various target organs. Accumulated experience shows that about 30 % of patients require combination therapy with 3 drugs from different pharmacological classes. Efficacy of BP control in real clinical practice with the use of various doses of perindopril, indapamide, and amlodipine as components of taken once-daily triple fixed combination was assessed in the 3-months prospective observational open-label PETRA study. In this study data of office BP measurements and 24-hour ambulatory BP monitoring (ABPM) were obtained from 11209 ambulatory patients (47.6 % women) with AH. Initial mean office BP (BPmoff) was 156.58±16.10 / 91.56±9.33 mm Hg, AH duration - 9.48±7.19 years. After switching to triple fixed dose combination of perindopril, indapamide, and amlodipine BPmoff decreased by 24.81±15.47 / 11.41±9.90 mm Hg (p<0.0001). Doses of perindopril, indapamide, and amlodipine in combination at the final visit were 5 / 1.25 / 5, 10 / 2.5 / 5, and 10 / 2.5 / 10 mg. 24-hour ambulatory BP monitoring (ABPM) was carried out in 76 patients. Mean 24-hour BP lowed from mean 155.51±17.43 / 85.28±11.48 down to 134.63±12.51 / 77.83±8.99 mm Hg (p<0.0001). Clinically relevant improvement of a number of parameters of metabolism occurred after 3 months of the study (in particular, lowering of levels of total and low-density lipoprotein cholesterol [-8.6 and - 11.4 %, respectively], triglycerides [-12,1 %], fasting blood glucose [-6.6 %]). Thus, results of the PETRA study confirmed 24-hour long antihypertensive efficacy of triple fixed dose combination of perindopril, indapamide, and amlodipine. This drug combination can present novel possibility in treatment of patients with AH who have not achieved target BP values on preceding dual combination therapy and fully corresponds with the single pill concept for formation of adherence to therapy.


Studies on binding sites, contents, and effects of AVP in isolated bladder and urethra from rabbits and humans.
The binding sites, contents, and effects of arginine vasopressin (AVP) were studied in isolated bladder and urethral preparations from rabbits and humans. In all tissues, higher levels of AVP-like immunoreactivity (AVP-LI) were detected than those normally found in plasma. Radioligand membrane binding studies using [3H]AVP as the ligand revealed the existence of a single population of binding sites in the rabbit bladder, and displacement experiments indicated that the receptor was of the V1 subtype. By autoradiography, [3H]AVP binding sites in the rabbit bladder were shown to be located on both circularly and longitudinally oriented smooth muscle cells, as well as in the submucosa at the part adjacent to the urothelium. In the rabbit urethra, the binding sites were confined mainly to the circular smooth muscle layer. Neither radioligand membrane binding studies nor autoradiography revealed any specific [3H]AVP binding sites in the human bladder. AVP contracted rabbit bladder and urethral preparations concentration dependently. The contractions were inhibited by the V1-receptor selective antagonist A16 in a noncompetitive manner. However, A16 had no effects on contractions elicited by electrical-field stimulation. In preparations of the human bladder and urethra, AVP in concentrations up to 10(-5) M did not have any contractile effects. These results suggest that in the rabbit and human lower urinary tract, AVP-LI is synthesized locally and/or extracted from the circulation. It is unlikely that AVP is directly involved in the neurotransmission in these tissues, although in the rabbit bladder and urethra a modulatory role cannot be excluded.


Noninvasive Cuffless Blood Pressure Estimation Using Pulse Transit Time and Impedance Plethysmography.
To demonstrate the feasibility of everaging impedance plethysmography (IPG) for detection of pulse transit time (PTT) and estimation of blood pressure (BP). We first established the relationship between BP, PTT, and arterial impedance (i.e., the IPG observations). The IPG sensor was placed on the wrist while the photoplethysmography sensor was attached to the index finger to measure the PTT. With a cuff-based BP monitoring system placed on the upper arm as a reference, our proposed methodology was evaluated on 15 young, healthy human subjects leveraging handgrip exercises to manipulate BP/PTT and compared to several conventional PTT models to assess the efficacy of PTT/BP detections. The proposed model correlated with BP fairly well with group average correlation coefficients of [Formula: see text] for systolic BP (SBP) and [Formula: see text] for diastolic BP (DBP). In comparison with the other PTT methods, PTT-IPG-based BP estimation provided a lower root-mean-squared-error of [Formula: see text] and [Formula: see text] for SBP and DBP, respectively. We conclude that the measurement of arterial impedance via IPG methods is an adequate indicator to estimate BP. The proposed method appears to offer superiority compared to the conventional PTT estimation approaches. Using impedance magnitude to estimate PTT offers promise to realize wearable and cuffless BP devices.


CXCR3 expression and activation of eosinophils: role of IFN-gamma-inducible protein-10 and monokine induced by IFN-gamma.
CXC chemokine receptor 3 (CXCR3), predominately expressed on memory/activated T lymphocytes, is a receptor for both IFN-gamma-inducible protein-10 (gamma IP-10) and monokine induced by IFN-gamma (Mig). We report a novel finding that CXCR3 is also expressed on eosinophils. gamma IP-10 and Mig induce eosinophil chemotaxis via CXCR3, as documented by the fact that anti-CXCR3 mAb blocks gamma IP-10- and Mig-induced eosinophil chemotaxis. gamma IP-10- and Mig-induced eosinophil chemotaxis are up- and down-regulated by IL-2 and IL-10, respectively. Correspondingly, CXCR3 protein and mRNA expressions in eosinophils are up- and down-regulated by IL-2 and IL-10, respectively, as detected using flow cytometry, immunocytochemical assay, and a real-time quantitative RT-PCR technique. gamma IP-10 and Mig act eosinophils to induce chemotaxis via the cAMP-dependent protein kinase A signaling pathways. The fact that gamma IP-10 and Mig induce an increase in intracellular calcium in eosinophils confirms that CXCR3 exists on eosinophils. Besides induction to chemotaxis, gamma IP-10 and Mig also activate eosinophils to eosinophil cationic protein release. These results indicate that CXCR3-gamma IP-10 and -Mig receptor-ligand pairs as well as the effects of IL-2 and IL-10 on them may be especially important in the cytokine/chemokine environment for the pathophysiologic events of allergic inflammation, including initiation, progression, and termination in the processes.


Identification of Riemerella anatipestifer genes differentially expressed in infected duck livers by the selective capture of transcribed sequences technique.
Riemerella anatipestifer is the causative agent of duck septicaemia. Determination of R. anatipestifer virulence mechanisms will help us to effectively control this contagious agent. The differentially expressed gene profile of R. anatipestifer in infected duck livers was therefore identified and compared with in vitro cultures by selective capture of transcribed sequences analysis. A total of 48 genes were identified, of which 43 were genes that encode enzymes for amino acid biosynthesis and metabolism, intermediary metabolism, and energy metabolism, or proteins for regulatory adaptive responses, general microbial stress response, transport proteins and secreted proteinases. Five were unknown, novel genes. Eight genes representing the categories were randomly chosen and verified by real-time reverse transcriptase-polymerase chain reaction analysis. All were upregulated by R. anatipestifer in infected duck livers, with changes ranging from 1.44-fold to 4.62-fold compared with in vitro cultures. The results from the present study revealed a gene expression profile of R. anatipestifer in infected duck livers. The unknown but novel genes may be potential novel virulence factors for R. anatipestifer. In conclusion, the data from this study will provide a molecular basis for further study of R. anatipestifer pathogenesis.


A comparison of subjective and physiological measures of mechanically produced and erotically produced erections (or, is an erection an erection?).
The current investigation explores possible reasons for the poor overall success rates of medical techniques used in the treatment of erectile dysfunction. This is the first study to compare directly the psychological impact of a mechanically produced versus an erotically produced erection. Subjective and objective parameters of sexual arousal were used to compare the experience of a mechanically attained erection versus an erotically stimulated erection. Twenty-eight (28) men without sexual dysfunction were asked to reach a full erection during each of the following two conditions: (a) by using an ErecAid System and (b) by self-stimulating while watching an erotic video. The results of this study suggest that the penile vacuum device was a successful method for attaining penile tumescence; however, the presence of penile tumescence was not accompanied by a subjective state of physical or mental sexual arousal. Thus, the mere physical presence of an erection does not seem to evoke bodily or mental feelings of sexual arousal. It is important to note that these findings suggest that attention to the psychosexual components of the individual's sexual experience are critical to the subjective experience of sexual arousal and reflect once again the multimodal response systems involved in sexual arousal. These results suggest that more effective treatment approaches would be based on a clinical strategy that provides instruction both on the technical use of a mechanical device as well as on the importance of creating an appropriate psychosexual environment.


Micronuclei: An essential biomarker in oral exfoliated cells for grading of oral squamous cell carcinoma.
Micronuclei in exfoliated oral epithelial cells have been shown in some studies to correlate with severity of this genotoxic damage. This severity can be measured in terms of grading of the lesions. To correlate frequency of micronuclei (MN) in oral exfoliated cells in clinically diagnosed cases of oral squamous cell carcinoma (OSCC) followed by a histopathological grading. The study subjects consisted of clinically diagnosed cases of OSCC. Healthy subjects without any tobacco consumption habits formed the control group. The cytosmears from both groups were stained with rapid Papanicolaou stain. MN were identified according to the criteria given by Countryman and Heddle with some modifications. The frequency of MN was three to four times higher in patients with OSCC as compared to patients in the control group and the difference was found to be highly significant. In 75% cases, the cytological grade as determined by the frequency of micronuclei correlated with the histopathological grade and this observation was statistically significant. MN can be a candidate to serve as a biomarker for prediction of the grade of OSCC.


Homogeneously staining chromosomal regions contain amplified copies of an abundantly expressed cellular oncogene (c-myc) in malignant neuroendocrine cells from a human colon carcinoma.
Two human neuroendocrine tumor cell lines derived from a colon carcinoma contain either numerous double minute chromosomes (COLO 320 DM) or a homogeneously staining marker chromosome (COLO 320 HSR). We found amplification and enhanced expression of the cellular oncogene c-myc in both COLO 320 DM and HSR cells, and we were able to show that the homogeneously staining regions of the COLO 320 HSR marker chromosome contain amplified c-myc. From previous and present karyotypes, it appears that the homogeneously staining regions reside on a distorted X chromosome. Therefore, amplification of c-myc has been accompanied by translocation of the gene from its normal position on chromosome 8 (8q24). Because double minute chromosomes were features of primary cultures from the original tumor, it seems reasonable to suspect that amplification of c-myc may have contributed to tumorigenesis.


Marker-trait association analysis for agronomic and compositional traits in sainfoin (Onobrychis viciifolia).
Sainfoin (Onobrychis viciifolia) is a perennial forage legume with great potential for use in sustainable agriculture due to its low input requirements, good drought tolerance, and production of forage rich in polyphenolic compounds, which are beneficial for animal health. However, its distribution and cultivation are limited due to its moderate agronomic performance and a general lack of well adapted, highly yielding cultivars. Faster progress in breeding is imperative, but is often hampered by the complex inheritance of traits and limited knowledge on the genetic composition of this tetraploid, outbreeding species. Molecular genetic tools might aid phenotypic selection; however, to date no information on marker-trait associations is available for sainfoin. Hence, the goal of the present study was to detect marker-trait associations in a biparental F1 population. Single plants were screened for recently developed genetic markers and phenotyped for important agronomic traits and concentrations of different polyphenolic compounds. Significant trait-associated markers (TAM) were detected for plant height (11), plant vigor (1), and seed yield (7). These three traits were positively correlated with each other and shared some TAMs. Correlations among markers suggested that two independent loci control these three vigor-related traits. One additional, independent TAM was detected for the share of prodelphinidins in total condensed tannins. Our results provide insight into the genetic control of important traits of sainfoin, and the TAMs reported here could assist selection in combination with phenotypic assessment.


The in vitro myelin formation in neurospheres of human neural stem cells.
To explore the culture conditions of human neural stem cells and to investigate the ultrastructure of neurospheres. The cells from the embryonic human cortices were mechanically dissociated. N2 medium was adapted to culture and expand the cells. The cells were identified by immunocytochemistry and EM was applied to examine the ultrastructure of neurospheres. The neural stem cells from human embryonic brains were successfully cultured and formed typical neurospheres in suspension, and most of the cells expressed vimentin, which was a marker for neural progenitor cells, and the cells could differentiate into neurons, astrocytes and oligodendrocytes. In vitro myelin formation in neurospheres were observed at an early stage of culture. Human neural stem cells can be cultured from embryonic brains, can form the typical neurospheres in suspension in vitro and have the ability of myelinating, and may be potential source for transplantation in treating myelin disorders.


An Overview of SARS-CoV-2 Etiopathogenesis and Recent Developments in COVID-19 Vaccines.
The Coronavirus disease-2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has significantly impacted the health and socioeconomic status of humans worldwide. Pulmonary infection of SARS-CoV-2 results in exorbitant viral replication and associated onset of inflammatory cytokine storm and disease pathology in various internal organs. However, the etiopathogenesis of SARS-CoV-2 infection is not fully understood. Currently, there are no targeted therapies available to cure COVID-19, and most patients are treated empirically with anti-inflammatory and/or anti-viral drugs, based on the disease symptoms. Although several types of vaccines are currently implemented to control COVID-19 and prevent viral dissemination, the emergence of new variants of SARS-CoV-2 that can evade the vaccine-induced protective immunity poses challenges to current vaccination strategies and highlights the necessity to develop better and improved vaccines. In this review, we summarize the etiopathogenesis of SARS-CoV-2 and elaborately discuss various types of vaccines and vaccination strategies, focusing on those vaccines that are currently in use worldwide to combat COVID-19 or in various stages of clinical development to use in humans.


Is adult stem cell aging driven by conflicting modes of chromatin remodeling?
Epigenetic control of gene expression by chromatin remodeling is critical for adult stem cell function. A decline in stem cell function is observed during aging, which is accompanied by changes in the chromatin structure that are currently unexplained. Here, we hypothesize that these epigenetic changes originate from the limited cellular capability to inherit epigenetic information. We suggest that spontaneous loss of histone modification, due to fluctuations over short time scales, gives rise to long-term changes in DNA methylation and, accordingly, in gene expression. These changes are assumed to impair stem cell function and, thus, to contribute to aging. We discuss cell replication as a major source of fluctuations in histone modification patterns. Gene silencing by our proposed mechanism can be interpreted as a manifestation of the conflict between the stem cell plasticity required for tissue regeneration and the permanent silencing of potentially deleterious genomic sequences.


Tell me what's wrong with me: a discourse analysis approach to the concept of patient autonomy.
Patient autonomy has gradually replaced physician paternalism as an ethical ideal. However, in a medical context, the principle of individual autonomy has different meanings. More knowledge is needed about what is and should be an appropriate understanding of the concept of patient autonomy in clinical practice. To challenge the traditional concept of patient autonomy by applying a discourse analysis to the issue. A qualitative case study approach with material from one consultation. The discourse is interpreted according to pragmatic and text-linguistic principles and provides the basis of a theoretical discussion of different concepts of patient autonomy. The consultation transcript illustrates how the patient's wishes can be respected in real life. The patient, her husband and the doctor are all involved in the discourse dynamics, governed by the subject matter, namely her mental illness. We suggest a dynamic and dialogue-based conception of autonomy as adequate for clinical purposes. These perspectives, based on mutual understanding, take communication between patient and doctor as their starting point. According to this approach, autonomy requires a genuine dialogue, an interpersonal mode of being which we choose to call "authentic interaction".


Transoral robotic surgery and transoral laser microsurgery for oropharyngeal squamous cell cancer.
The aim of our study was to compare transoral laser microsurgery (TLM) and transoral robotic surgery (TORS) for primary resection of oropharyngeal squamous cell cancer (OPSCC). This was a retrospective chart analysis of 33 patients with OPSCC treated at one academic medical center with either TORS (n = 17) or TLM (n = 16) between July 2008 and December 2010. Six patients in the TLM group and seven patients in the TORS group had primary cancer of the tonsil; the remaining patients had base of tongue cancer. Two patients in the TORS group had Stage I or II disease; the other 31 patients had Stage III [1/16 (6 %) TLM; 5/17 (29 %) TORS] or Stage IV cancer [15/16 (94 %) TLM; 10/17 (59 %) TORS]. The intervention was transoral surgery for OPSCC, and the main outcome measures were perioperative variables and functional outcomes. Mean operative time was 170 versus 115 min for TLM and TORS, respectively (p = 0.057). One patient, in the TLM group, required a temporary tracheostomy. Perioperative feeding tubes were placed in 6/16 (38 %) patients who underwent TLM and in 4/17 (24 %) patients who underwent TORS (p = 0.465). At a median follow-up of 14.5 months, the average MD Anderson Dysphagia Inventory score was 65.2 for TLM and 70.8 for TORS (p = 0.431). All TORS procedures were performed with a single oral retractor, while multiple laryngoscopes were required in 9/16 (56 %) TLM cases (p = 0.0003). The mean number of total specimens were 6.2 for TORS and 13.6 for TLM (p = 0.002). These results demonstrate that TLM and TORS have comparable perioperative variables with no significant differences in functional outcomes. For a subset of patients, TORS reduced the spatial complexity of surgery, suggested by the decreased need for multiple laryngoscopes, fewer specimens, and shorter operative times, while larger tumors were more amenable to TLM.


Unequal sister chromatid exchange. A mechanism affecting Ig gene arrangement and expression.
Two gamma 2a gene forms in the MPC11 mouse myeloma cell line (gamma 2b, K) have been localized to the expressed H chain chromosome, where they exist in tandem downstream of the expressed gamma 2b gene. The gamma 2a gene duplication has apparently occurred by spontaneous, unequal sister chromatid exchange (SCE) in a B lymphoid precursor of MPC11 or in MPC11 itself. It is especially significant that either of the tandem gamma 2a gene forms may be used in the class switch from gamma 2b to gamma 2a production occurring in the MPC11 line, indicating that heavy chain constant region (CH) gene duplication (or deletion) may be a mechanism normally impinging on CH gene expression. The gamma 2a genes of MPC11 undergo further copy number variation via unequal SCE in variants of this line derived by mutagenesis and selection for altered H chain production. The remarkable frequency with which copy number variation occurs in these cells suggests that unequal SCE may play a physiological role in CH gene arrangement and expression.


Rheum officinale (a traditional Chinese medicine) for chronic kidney disease.
Chronic kidney disease (CKD) is a major public health issue worldwide. Standard therapies to delay CKD progression include dietary protein restriction and administration of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) to help control blood pressure and confer additional renoprotective effects. Despite such interventions, CKD incidence and mortality rates continue to increase. Rheum officinale (Da Huang) a medicinal herb used widely in China to treat CKD has been reported to offer a range of pharmacological properties that may delay disease progression. To assess the benefits and harms of Rheum officinale for preventing the progression of CKD. We searched the Cochrane Renal Group's Specialised Register and CENTRAL (Issue 4, 2011), MEDLINE, EMBASE, the Chinese Biomedicine Database (CBM), China National Knowledge Infrastructure (CNKI), VIP (Chongqing VIP Chinese Science and Technology Periodical Database), and Wanfang Data. We also handsearched reference lists of articles. We applied no restrictions on language of publication. We included randomised controlled trials (RCTs) and quasi-RCTs that assessed the benefits and harms of Rheum officinale for preventing the progression of CKD regardless of dosage, type, maturity, mode of administration, duration of treatment, or storage time before use. Two authors independently screened titles and abstracts for eligibility, assessed study quality, and extracted data. We expressed results for dichotomous outcomes (need for renal replacement therapy, all-cause mortality, quality of life) as risk ratios (RR) with 95% confidence intervals (CI). Continuous outcomes (glomerular filtration rate (GFR), serum creatinine (SCr), creatinine clearance (CrCl), blood urea nitrogen (BUN)) were expressed as mean differences (MD) with 95% CIs. We identified nine studies that enrolled 682 participants. None of the studies reported blinding or group allocation methods. Seven studies were judged to be at low risk of incomplete outcome reporting; three studies were judged to be a low risk of selective reporting (protocols were available and/or all outcomes relevant to the this review were reported); and two studies were judged free of other potential biases.Seven studies compared Rheum officinale with no treatment and two made comparisons with captopril, an angiotensin-converting enzyme inhibitor (ACEi). Compared with no treatment, Rheum officinale had a positive effect on SCr (MD -87.49 µmol/L, 95% CI -139.25 to -35.72) and BUN (MD -10.61 mmol/L, 95% CI -19.45 to -2.21). Compared with captopril, a statistically significant difference was not demonstrated in relation to Rheum officinale for any outcome (BUN, CrCl, or patients' capacity to undertake work). No data were available on all-cause mortality or cost of treatment. Only minor adverse events were reported in association with Rheum officinale. Currently available evidence concerning the efficacy of Rheum officinale to improve SCr and BUN levels in patients with CKD is both scant and low quality. Although Rheum officinale does not appear to be associated with serious adverse events among patients with CKD, there is no current evidence to support any recommendation for its use.


Studies with Human-Induced Pluripotent Stem Cells Reveal That CTNS Mutations Can Alter Renal Proximal Tubule Differentiation.
Cystinosis is an autosomal recessive disease resulting from mutations in ctns, which encodes for cystinosin, a proton-coupled cystine transporter that exports cystine from lysosomes. The major clinical form, infantile cystinosis, is associated with renal failure due to the malfunctioning of the renal proximal tubule (RPT). To examine the hypothesis that the malfunctioning of the cystinotic RPT arises from defective differentiation, human-induced pluripotent stem cells (hiPSCs) were generated from human dermal fibroblasts from an individual with infantile cystinosis, as well as a normal individual. The results indicate that both the cystinotic and normal hiPSCs are pluripotent and can form embryoid bodies (EBs) with the three primordial germ layers. When the normal hiPSCs were subjected to a differentiation regime that induces RPT formation, organoids containing tubules with lumens emerged that expressed distinctive RPT proteins, including villin, the Na+/H+ Exchanger (NHE) isoform 3 (NHE3), and the NHE Regulatory Factor 1 (NHERF1). The formation of tubules with lumens was less pronounced in organoids derived from cystinotic hiPSCs, although the organoids expressed villin, NHE3, and NHERF1. These observations can be attributed to an impairment in differentiation and/or by other defects which cause cystinotic RPTs to have an increased propensity to undergo apoptosis or other types of programmed cell death.


The role of an intensive care unit in a community hospital. A ten-year review with observations on utilization past, present, and future.
A retrospective ten-year review of the surgical-intensive-care-unit utilization practices at Riverside Community Hospital revealed that, according to the author's criteria, an average of 32% of over 800 yearly admissions could have been safely managed in a less intensive and expensive environment. The admission practices, monitoring parameters, length of stay, and intensity of nursing interaction were evaluated and compared with those of published reports. Prospective payment by diagnosis-related groups will likely force a change in the existing use of surgical intensive care units. Surgeons are urged to examine the utilization of their hospitals' intensive care units and actively work with their hospital administration to establish intermediate care units so that patients will not be jeopardized by the impending fiscal constraints of diagnosis-related groups.


Body weight dissatisfaction and communication with parents among adolescents in 24 countries: international cross-sectional survey.
Parents have significant influence on behaviors and perceptions surrounding eating, body image and weight in adolescents. The aim of this study was to examine the prevalence of body weight dissatisfaction, difficulty in communication with the parents and the relationship between communication with parents and adolescents' dissatisfaction with their body weight (dieting or perceived need to diet). Survey data were collected from adolescents in 24 countries and regions in Europe, Canada, and the USA who participated in the cross-sectional 2001/2002 Health Behaviour of School-Aged Children (HBSC) study. The association between communication with parents and body weight dissatisfaction was examined using binary logistic regression analysis. Body weight dissatisfaction was highly prevalent and more common among girls than boys, among overweight than non-overweight, and among older adolescents than younger adolescents. Difficulty in talking to father was more common than difficulty in talking to mother in all countries and it was greater among girls than among boys and increased with age. Difficulties in talking to father were associated with weight dissatisfaction among both boys and girls in most countries. Difficulties in talking to mother were rarely associated with body weight dissatisfaction among boys while among girls this association was found in most countries. The findings suggest that enhanced parent communication might contribute in most countries to less body dissatisfaction in girls and better communication with the father can help avoiding body weight dissatisfaction in boys. Professionals working with adolescents and their families should help adolescents to have a healthy weight and positive body image and promote effective parent-adolescent communication.


The malignancy of miR-18a in human glioblastoma via directly targeting CBX7.
Aberrant levels of microRNAs (miRNAs) are linked to tumorigenesis and tumor progression. Here we analyzed the expression of microRNA 18a in glioblastoma multiforme (GBM) within groups of coexpressed groups of genes through analysis of expression profiling databases and clinical tissues. Cell proliferation and flow cytometry experiments were performed to determine the roles of miR-18a in the proliferation of glioblastoma cells in vitro. We employed bioinformatics analyses, luciferase reporter assays, and immunoblotting to identify chromobox protein homolog 7 (CBX7) as the target gene of miR-18a. A significant inverse correlation was observed between miR-18a and CBX7 expression in GBM tissues (r = -0.6264, P = 0.0094). Bioinformatics analyses revealed that most CBX7-associated genes were enriched in terms associated with cell cycle pathways. Upregulated expression of CBX7 inhibited the growth of GBM cells and reduced the expression of CDK2 and cyclin A2 (CCNA2). Rescue experiments indicated that overexpression of CBX7 significantly recovered the increase in cell proliferation and cell cycle distribution induced by miR-18a overexpression. In vivo studies revealed that decreased levels of miR-18a delayed the growth of intracranial tumors, which was accompanied by increased CBX7 expression. We suggest that miR-18a promotes glioblastoma progression via altering CBX7 expression and therefore may serve as a potential target for treating glioblastoma.


In situ probing the interior of single bacterial cells at nanometer scale.
We report a novel approach to probe the interior of single bacterial cells at nanometre resolution by combining focused ion beam (FIB) and atomic force microscopy (AFM). After removing layers of pre-defined thickness in the order of 100 nm on the target bacterial cells with FIB milling, AFM of different modes can be employed to probe the cellular interior under both ambient and aqueous environments. Our initial investigations focused on the surface topology induced by FIB milling and the hydration effects on AFM measurements, followed by assessment of the sample protocols. With fine-tuning of the process parameters, in situ AFM probing beneath the bacterial cell wall was achieved for the first time. We further demonstrate the proposed method by performing a spatial mapping of intracellular elasticity and chemistry of the multi-drug resistant strain Klebsiella pneumoniae cells prior to and after it was exposed to the 'last-line' antibiotic polymyxin B. Our results revealed increased stiffness occurring in both surface and interior regions of the treated cells, suggesting loss of integrity of the outer membrane from polymyxin treatments. In addition, the hydrophobicity measurement using a functionalized AFM tip was able to highlight the evident hydrophobic portion of the cell such as the regions containing cell membrane. We expect that the proposed FIB-AFM platform will help in gaining deeper insights of bacteria-drug interactions to develop potential strategies for combating multi-drug resistance.


Control of Saccharomyces cerevisiae pre-tRNA processing by environmental conditions.
tRNA is essential for translation and decoding of the proteome. The yeast proteome responds to stress and tRNA biosynthesis contributes in this response by repression of tRNA transcription and alterations of tRNA modification. Here we report that the stress response also involves processing of pre-tRNA 3' termini. By a combination of Northern analyses and RNA sequencing, we show that upon shift to elevated temperatures and/or to glycerol-containing medium, aberrant pre-tRNAs accumulate in yeast cells. For pre-tRNAUAU(Ile) and pre-tRNAUUU Lys) these aberrant forms are unprocessed at the 5' ends, but they possess extended 3' termini. Sequencing analyses showed that partial 3' processing precedes 5' processing for pre-tRNAUAU(Ile). An aberrant pre-tRNA(Tyr) that accumulates also possesses extended 3' termini, but it is processed at the 5' terminus. Similar forms of these aberrant pre-tRNAs are detected in the rex1Δ strain that is defective in 3' exonucleolytic trimming of pre-tRNAs but are absent in the lhp1Δ mutant lacking 3' end protection. We further show direct correlation between the inhibition of 3' end processing rate and the stringency of growth conditions. Moreover, under stress conditions Rex1 nuclease seems to be limiting for 3' end processing, by decreased availability linked to increased protection by Lhp1. Thus, our data document complex 3' processing that is inhibited by stress in a tRNA-type and condition-specific manner. This stress-responsive tRNA 3' end maturation process presumably contributes to fine-tune the levels of functional tRNA in budding yeast in response to environmental conditions.


Coverage of large pediatric wounds with cultured epithelial autografts in congenital nevi and burns: results and technique.
The use of cultured epithelial autografts (CEA) for the treatment of large burn wounds has gained popularity in recent years. This technique may circumvent the restrictions of limited donor site availability and hasten permanent wound coverage for large TBSA burns. The availability of a large amount of skin from a small donor site with the promise of permanent wound coverage suggests its use in other conditions such as giant congenital nevi (GCN) as well. The risk of malignant transformation of GCN to melanoma although somewhat controversial is significant enough to warrant early excision in childhood. Cultured keratinocytes may provide one-stage coverage of these large wounds, lessening the number of surgeries and the inherent staging problems of tissue expansion or autografting. A retrospective single institution review of was done for 29 children (20 burns and 9 patients with GCN) who underwent coverage of their large surface area wounds with CEA over an 18-year period. Excellent take rates were noted; 76.4% for burn patients and 66% for patients with GCN. Several strategies in preoperative, perioperative, and postoperative care have been standardized and have helped improve outcome. The keys to success with the CEA technique have been aggressive control of wound sepsis, surgical technique, specific use of topical antimicrobials, dressings, and the standardization of nursing and physiotherapy care. Although the cost of CEA is high, the benefits to patient care make this technique an appealing choice for large wound coverage in the pediatric population.


Predictive Factors and Duration to Return to Sport After Isolated Meniscectomy.
Return to sport (RTS) after meniscectomy is an important metric for young, active patients. However, the impact of the duration from surgery to RTS on clinical outcomes is not fully understood and is not reflected in outcome scores. To establish when patients RTS after meniscectomy and to determine predictive measures for the ability to return to their preinjury activity. Case-control study; Level of evidence, 3. All patients undergoing meniscectomy between 2016 and 2017 from a single institution were assessed for inclusion. RTS, type of activity, and level of function upon returning were obtained. The minimal clinically important difference (MCID), substantial clinical benefit, and patient acceptable symptom state (PASS) were calculated for the Knee injury and Osteoarthritis Outcome Score (KOOS) and International Knee Documentation Committee (IKDC) questionnaire using anchor-based and distribution-based approaches. Preoperative knee-specific and generic quality-of-life scores were analyzed to determine their predictive power of RTS. A multivariate logistical analysis was also performed to determine which demographic variables corresponded to RTS. Overall, 94 patients (mean age, 51.0 ± 11.1 years) who underwent meniscectomy participated in sports within 6 months of surgery. Of these patients, 76.6% returned to sport without permanent restrictions at a mean of 8.6 ± 6.9 weeks postoperatively. RTS rates for low-, medium-, and high-intensity activities were 75.0%, 70.0%, and 82.5%, respectively. RTS was associated with achieving the PASS for the KOOS-Physical Function short form (PS), KOOS-Pain, and KOOS-Sports (P = .004, P = .007, and P = .006, respectively) but not for the IKDC questionnaire (P = .3). Achieving the MCID was associated with RTS for the KOOS-Sports, KOOS-Pain, and IKDC questionnaire (P < .001, P = .03, and P = .001, respectively). There was no preoperative or intraoperative variable that was predictive of RTS. Preoperative KOOS-PS scores ≥37.8 (area under the curve = 76.3%) and KOOS-Pain scores ≥51.4 (area under the curve = 72.5%) were predictive of RTS. Approximately 77% of patients returned to sport after meniscectomy at a mean of 2 months postoperatively. The level of activity intensity did not significantly alter the rate of RTS. Higher preoperative scores on the KOOS-PS and KOOS-Pain were predictive of RTS. Identifying these factors allows physicians to counsel patients on expected outcomes after meniscectomy.


Review of nanomaterial aging and transformations through the life cycle of nano-enhanced products.
In the context of assessing potential risks of engineered nanoparticles (ENPs), life cycle thinking can represent a holistic view on the impacts of ENPs through the entire value chain of nano-enhanced products from production, through use, and finally to disposal. Exposure to ENPs in consumer or environmental settings may either be to the original, pristine ENPs, or more likely, to ENPs that have been incorporated into products, released, aged and transformed. Here, key product-use related aging and transformation processes affecting ENPs are reviewed. The focus is on processes resulting in ENP release and on the transformation(s) the released particles undergo in the use and disposal phases of its product life cycle for several nanomaterials (Ag, ZnO, TiO2, carbon nanotubes, CeO2, SiO2 etc.). These include photochemical transformations, oxidation and reduction, dissolution, precipitation, adsorption and desorption, combustion, abrasion and biotransformation, among other biogeochemical processes. To date, few studies have tried to establish what changes the ENPs undergo when they are incorporated into, and released from, products. As a result there is major uncertainty as to the state of many ENPs following their release because much of current testing on pristine ENPs may not be fully relevant for risk assessment purposes. The goal of this present review is therefore to use knowledge on the life cycle of nano-products to derive possible transformations common ENPs in nano-products may undergo based on how these products will be used by the consumer and eventually discarded. By determining specific gaps in knowledge of the ENP transformation process, this approach should prove useful in narrowing the number of physical experiments that need to be conducted and illuminate where more focused effort can be placed.


Network Synthesis through Data-Driven Growth and Decay.
AN ALGORITHM FOR ADDITION AND DELETION (ADDEL) OF RESOURCES DURING LEARNING IS DEVELOPED TO ACHIEVE TWO GOALS: (1) to find feed-forward multilayer networks that are as small as possible, (2) to find an appropriate structure for such small networks. These goals are accomplished by operating alternately between an adding phase and a deleting phase while learning the given input-output associations. The adding phase develops a crude structure by filling in resources (connections, units and layers) at a virtual multilayer network with a maximum of L possible layers. The deleting phase then removes any unnecessary connections to obtain a refined structure. The additions and deletions are done based on a sensitivity measure and a corresponding probability rule so that only the synapses which are most effective in reducing the output error are preserved. A generalization error estimated from a validation set is used to control the alternation between the two learning phases and the termination of learning. Simulations, including handwritten digit recognition, demonstrate that the algorithm is effective in finding an appropriate network structure for a small network which can generalize well. The algorithm is used to investigate when the size of a network is important for generalization. Copyright 1997 Elsevier Science Ltd.


Unusual mechanism of tendoachilles injury.
A 67-year-old woman sustained electric shock while using her hair dryer. During this process her left leg shot up in the air following which she could not walk properly with that leg. She attended the accident and emergency and, considering a possibility of an undisplaced fracture of the calcaneum, she was referred to the fracture clinic the next day. She was clinically diagnosed to have tendoachilles rupture and this was further confirmed by an ultrasound scan. Predisposing factors like drug intake or chronic inflammatory arthritis were excluded and she was treated with conservative management.


A Systematic Approach for Developing Bacteria-Specific Imaging Tracers.
The modern patient is increasingly susceptible to bacterial infections including those due to multidrug-resistant organisms (MDROs). Noninvasive whole-body analysis with pathogen-specific imaging technologies can significantly improve patient outcomes by rapidly identifying a source of infection and monitoring the response to treatment, but no such technology exists clinically. We systematically screened 961 random radiolabeled molecules in silico as substrates for essential metabolic pathways in bacteria, followed by in vitro uptake in representative bacteria-Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and mycobacteria. Fluorine-labeled analogs, that could be developed as PET-based imaging tracers, were evaluated in a murine myositis model. We identified 3 novel, nontoxic molecules demonstrating selective bacterial uptake: para-aminobenzoic acid (PABA), with uptake in all representative bacteria including Mycobacterium tuberculosis; mannitol, with selective uptake in S. aureus and E. coli; and sorbitol, accumulating only in E. coli None accumulated in mammalian cells or heat-killed bacteria, suggesting metabolism-derived specificity. In addition to an extended bacterial panel of laboratory strains, all 3 molecules rapidly accumulated in respective clinical isolates of interest including MDROs such as methicillin-resistant S. aureus, extended-spectrum β-lactamase-producing, and carbapenem-resistant Enterobacteriaceae. In a murine myositis model, fluorine-labeled analogs of all 3 molecules could rapidly detect and differentiate infection sites from sterile inflammation in mice (P = 0.03). Finally, 2-deoxy-2-[F-18]fluoro-d-sorbitol (18F-FDS) can be easily synthesized from 18F-FDG. PET, with 18F-FDS synthesized using current good manufacturing practice, could rapidly differentiate true infection from sterile inflammation to selectively localize E. coli infection in mice. We have developed a systematic approach that exploits unique biochemical pathways in bacteria to develop novel pathogen-specific imaging tracers. These tracers have significant potential for clinical translation to specifically detect and localize a broad range of bacteria, including MDROs.


Nucleotide sequence of the respiratory syncytial virus phosphoprotein gene.
A cDNA library was prepared from poly(A)+ RNA extracted from respiratory syncytial (RS) virus-infected HEp-2 cells. A recombinant plasmid, pRSP68, encoding the RS virus phosphoprotein gene was identified by translation in vitro of hybrid-selected mRNA. The cloned cDNA insert of 1 kb was sequenced and a polypeptide of 241 amino acids with a molecular weight of 27 166 was deduced from the sequence. The protein was relatively rich in polar amino acids and devoid of both cysteine and tryptophan. A second short open reading frame with a coding potential of 65 amino acids was identified and overlapped the 3' terminus of the phosphoprotein gene by 34 bases.


Induction of twin pregnancy and the risk of caesarean delivery: a cohort study.
Complications are common in twin pregnancies and induction of labour is often indicated. Most methods for induction are used but data on risks related to induction methods are sparse. The aim of this study was to investigate the association between induction of labour and caesarean delivery in twin pregnancies, and to assess the influence of induction method. Cohort study of twin pregnancies ≥ 34 weeks, planned for vaginal delivery, from two University Hospitals in Sweden. Data were collected from medical records during the periods 1994 (Örebro) and 2004 (Uppsala) to 2013. During the study period there were 78,180 live born births and 1,282 were twin births. Women with previous caesarean section were excluded. Induction methods were categorized into amniotomy, oxytocin and cervical ripening (intra cervical Foley catheter or prostaglandin). Adjusted odds ratios (AOR) with 95 % confidence interval (CI) for caesarean section were calculated by logistic regression and were adjusted for parity, maternal age, gestational length, complications to the pregnancy, infant birth weight and year of birth. Spontaneous labour onsets were used as the reference group. The main outcome measure was caesarean section. In 462 twin pregnancies, 220 (48 %) had induction of labour and 242 (52 %) a spontaneous labour onset. Amniotomy was performed in 149 (68 %) of these inductions, oxytocin was administered in 11 (5 %) and cervical ripening was used in 60 (27 %). The rate of caesarean sections was 21 % in induced and 12 % in spontaneous labours (p 0.01). The absolute risk of caesarean section following induction was: 15 % with amniotomy; 36 % with oxytocin and 37 % with Foley/prostaglandin. Induction of labour increased the risk of caesarean section by 90 % compared with spontaneous labour onset (AOR 1.9, 95 % CI 1.1-3.5) and, when cervical ripening was used, the risk increased more than two fold (AOR 2.5, 95 % CI 1.2-5.3). Induction of labour in twin pregnancies increases the risk of caesarean section compared with spontaneous labour onset, especially if Foley catheter or prostaglandins are required. However, approximately 80 % of induced labours are delivered vaginally.


Aqueous extract of Phyllanthus urinaria induces apoptosis in human cancer cells.
Cell apoptosis is now known to play an important role in the maintenance of cellular homeostasis and anti-carcinogenesis. The anticancer effect of aqueous extract prepared from Phyllanthus urinaria (P. urinaria) was investigated by analyzing its potential to induce apoptosis in human cancer cells. We showed that the aqueous extract of P. urinaria could reduce the viability by inducing the apoptosis in human cancer cells derived from several different origins as demonstrated by morphological changes and DNA fragmentation. Yet, P. urinaria extract exhibited no cytotoxic effect on normal human cells, including vascular endothelial cells and liver cells under the same conditions. It suggests that the aqueous extract of P. urinaria is substantially useful in treating various kinds of human cancer cells without toxic side effect on normal cells.


Effects of parenteral administration of vitamin E on health of periparturient dairy cows.
To determine the effect of administration of vitamin E (D-alpha-tocopherol) on the incidence of retained placenta, metritis, and clinical mastitis during early lactation and on tocopherol concentrations. Prospective randomized controlled study. 420 Holstein cows. Vitamin E (3,000 mg, IM, once) was administered to 204 cows B to 14 days before expected parturition, and 216 control cows were not treated. The number of cows that had retained placenta, metritis, clinical mastitis, displaced abomasum, and clinically apparent acetonemia or hypocalcemia were recorded. Serum concentrations of tocopherol, the tocopherol:cholesterol ratio, and glutathione-peroxidase activity were determined from samples obtained before administration of vitamin E, 7 and 14 days after administration, and at 30 days after parturition from 36 treated and 36 control cows. Administration of vitamin E significantly decreased the incidence of retained placenta and metritis (13/204 [6.4%] and 8/204: [3.9%], respectively, for the vitamin E-treated group; 27/216 [12.5%] and 19/ 216 [8.8%], respectively, for the untreated group) but did not affect the incidence of clinical mastitis. Serum vitamin E concentration was significantly higher in treated than in control cattle at 7 and 14 days after administration, but serum tocopherol: cholesterol ratio was significantly higher only at 7 days after administration. Parenteral administration of a single injection of vitamin E before parturition may decrease the incidence of retained placenta and metritis in dairy cows but will increase serum concentrations for 7 to 14 days after administration.


Diversity, virulence and antibiogram traits of Escherichia coli recovered from potable water sources in Gharbia, Egypt.
This study aimed to assess the public health risk of coliforms and Escherichia coli contamination of potable water sources in Egypt. A total of 150 water samples (100 tap and 50 well) were collected from five districts in Gharbia governorate, Egypt. High rates of coliforms contamination were recorded in 52 and 76% of examined tap and well water samples, respectively. E. coli strains were detected in 16% of the water samples (15% tap water and 18% well water; 23.7% rural and 8.1% urban). Rural water sources were 3.5 times more likely to be contaminated than urban sources (P = 0.01). Eight (33.3%) E. coli isolates were Shiga toxin-producing E. coli (STEC). Multiple drug resistance (MDR) was observed for 62.5% of the isolates. Seven (29.2%) E. coli isolates harboured at least one of the extended-spectrum beta-lactamase (ESBL) genes. The majority (87.5%) of the STEC isolates were MDRs and harboured ESBL genes. STEC isolates were significantly more likely to resist six classes of antibiotics than non-STEC isolates. This is the first report of potable water contamination with MDR-STEC in Egypt. This study highlights an alarming public health threat that necessitates preventive interventions for public and environmental safety.


Leptomeningeal carcinomatosis of gastric cancer misdiagnosed as vestibular schwannoma.
Gastric cancer is one of the most common causes of cancer-related death in Asian countries, including Korea. We experienced a case of leptomeningeal carcinomatosis (LC) from gastric cancer that was originally misdiagnosed as vestibular schwannoma based on the similar radiological characteristics. To our knowledge, LC from gastric cancer is very rare. In conclusion, our experience with this case suggests that clinicians should consider the possibility of delayed leptomeningeal metastasis when treating patients with gastric cancer.


Using highly emissive and environmentally sensitive o-carborane-functionalized metallophosphors to monitor mitochondrial polarity.
Mitochondria as vital intracellular organelles play critical roles in multiple physiological processes, and their polarity is a crucial characteristic that can reveal the intracellular environment and impact cellular events. In this work, we designed and synthesized a novel series of highly emissive and environmentally sensitive phosphorescent iridium(iii) complexes (2a-2e, 3a-3e and 4) functionalized by o-carborane. These complexes showed high emission quantum yields both in solution and in solid state (up to ΦPL = 0.82), long emission lifetime and tunable emission wavelength over 74 nm by introduction of a carboranyl motif in their ligands. Importantly, all the complexes have shown significant solvatochromic effects in contrast to the carborane-free control complex. Among them, complex 2d shows the highest sensitivity to polarity of solvents with a MPPS (maximum peak phosphorescence shift) value of 42 nm and clear dependence of phosphorescence lifetime on solvent polarity. Interestingly, complex 2d can easily penetrate into cells and preferentially distribute in mitochondria. To utilize these properties, the first phosphorescent imaging of mitochondrial polarity has been realized by photoluminescence lifetime imaging microscopy (PLIM), which can monitor mitochondria-relevant cellular processes such as cell apoptosis and distinguish cancer cells from normal cells. Compared to intensity-based sensing, lifetime-based detection is independent of the probe concentration, excitation power and photobleaching of probes, which can show high accuracy and reproducibility.


Review of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds.
The roots and rhizomes of licorice (Glycyrrhiza) species have long been used worldwide as a herbal medicine and natural sweetener. Licorice root is a traditional medicine used mainly for the treatment of peptic ulcer, hepatitis C, and pulmonary and skin diseases, although clinical and experimental studies suggest that it has several other useful pharmacological properties such as antiinflammatory, antiviral, antimicrobial, antioxidative, anticancer activities, immunomodulatory, hepatoprotective and cardioprotective effects. A large number of components have been isolated from licorice, including triterpene saponins, flavonoids, isoflavonoids and chalcones, with glycyrrhizic acid normally being considered to be the main biologically active component. This review summarizes the phytochemical, pharmacological and pharmacokinetics data, together with the clinical and adverse effects of licorice and its bioactive components.


The inflammatory molecules IL-1β and HMGB1 can rapidly enhance focal seizure generation in a brain slice model of temporal lobe epilepsy.
Epilepsy is a neurological disorder characterized by a hyperexcitable brain tissue and unpredictable seizures, i.e., aberrant firing discharges in large neuronal populations. It is well established that proinflammatory cytokines, in addition to their canonical involvement in the immune response, have a crucial role in the mechanism of seizure generation. The purpose of the present study was to investigate the role of interleukin-1β (IL-1β) and high mobility group B1 (HMGB1) in the generation of seizure-like discharges using two models of focal epilepsy in a rat entorhinal cortex slice preparation. Seizure like-discharges were evoked by either slice perfusion with low Mg(2+) and picrotoxin or with a double NMDA local stimulation in the presence of the proconvulsant 4-amino-pyridine. The effects of IL-1β or HMGB1 were evaluated by monitoring seizure discharge generation through laser scanning microscope imaging of Ca(2+) signals from neurons and astrocytes. In the picrotoxin model, we revealed that both cytokines increased the mean frequency of spontaneous ictal-like discharges, whereas only IL-1β reduced the latency and prolonged the duration of the first ictal-like event. In the second model, a single NMDA pulse, per se ineffective, became successful when it was performed after IL-β or HMGB1 local applications. These findings demonstrate that both IL-1β and HMGB1 can rapidly lower focal ictal event threshold and strengthen the possibility that targeting these inflammatory pathways may represent an effective therapeutic strategy to prevent seizures.


Serum 25-Hydroxy Vitamin D, Vitamin B12, and Folic Acid Levels in Progressive and Nonprogressive Keratoconus.
To evaluate the serum 25-hydroxy vitamin D, vitamin B12, and folic acid (FA) levels in progressive and nonprogressive patients with keratoconus (KCN). Fifty-five patients with KCN (28 progressive and 27 nonprogressive) who were followed up for at least 12 months were recruited and separated into 2 groups according to corneal topographic progression criteria. Age- and sex-matched 30 healthy individuals formed the control group. Serum vitamin D, B12, FA, and Ca levels were compared among control, nonprogressive, and progressive groups. The effect of gender, age, vitamin D, B12, and FA parameters on KCN progression was investigated. Serum vitamin D levels were 12.77 ± 5.52, 11.78 ± 4.32, and 17.40 ± 5.12 ng/mL in nonprogressive, progressive, and control groups, respectively. The serum vitamin D levels in KCN groups (nonprogressive and progressive) were significantly lower than the control group (P = 0.002 and P < 0.001, respectively). There was no significant difference between all groups in serum vitamin B12, FA, and Ca levels (P > 0.05). Decreased vitamin D levels significantly increased nonprogressive KCN probability 1.23 times and progressive KCN probability 1.29 times more than the control group (P = 0.002, 95% confidence interval, 0.708-0.925; P < 0.001, 95% confidence interval, 0.668-0.888, respectively). Serum vitamin D levels were significantly decreased in both KCN groups. However, serum vitamin B12, FA, and Ca levels were similar in all groups. Serum vitamin D evaluation of patients with KCN at onset and follow-up examinations may help to predict the course of the disease.


Successful use of anti-retroviral therapy in combination with cytotoxic chemotherapy for persistent molar pregnancy: a case report.
Due to the HIV pandemic, the chances of finding gynecological malignancies in HIV-infected women are increased. This poses management and ethical dilemmas as the treatment for such malignancies are likely to further decrease their immunity. Gestational trophoblastic disease occurs predominantly among young women and has excellent response to chemotherapy. However, such therapy is not possible if their immunity (CD4 counts) is markedly depressed. The patient described presented with persistent molar pregnancy and had low CD4 count. She was given antiretroviral therapy and once the CD4 count had risen to acceptable levels cytotoxic chemotherapy was administered. She received a total of 13 cycles of chemotherapy with no significant untoward effects. After a 6-month follow-up period the patient was well with a negative serum betaHCG level and CD4 count above 200. We conclude that HIV-infected women with gestational trophoblastic disease may be safely treated with cytotoxic chemotherapy provided anti-retroviral therapy is concurrently administered to boost immunity.


Respiratory burst enzyme in human neutrophils. Evidence for multiple mechanisms of activation.
Alteration of the surface of human neutrophils with the nonpenetrating, protein-inactivating agent p-diazobenzenesulfonic acid (DASA) was found to prevent activation of the respiratory burst by some stimuli, but not others. Production of superoxide anion (O2-) stimulated by concanavalin A or the chemotactic peptide formyl-methionyl-leucyl-phenylalanine FMLP was inhibited by DASA pretreatment, whereas O2- production stimulated by phorbol myristate acetate (PMA), sodium fluoride. or the ionophore A23187 was not inhibited by DASA. Pretreatment with DASA inhibited oxygen uptake stimulated by FMLP, but not oxygen uptake stimulated by PMA. DASA reproducibly inhibited activities of two known surface enzymes Mg++-ATPase and alkaline phosphatase, by 45-55% and 60-70%, respectively. The inhibition by DASA of O2- production did not appear to be caused by interference with binding of the affected stimuli, since pretreatment with DASA did not inhibit release of the lysosomal enzymes lysozyme and myeloperoxidase induced by concanavalin A or FMLP. Membrane-rich particulate fractions from neutrophils have been shown to contain NADPH-dependent oxidative activity that is presumably responsible for the phagocytosis-associated respiratory burst of intact cells. The PMA-activated enzyme was susceptible to inhibition of directly exposed to DASA in this particulate fraction. These findings suggest that more than one mechanism exists for activation of the respiratory burst oxidase in human neutrophils, and that the neutrophil possesses at least one oxidase that is not an ectoenzyme.


Monoclonal antibody screening of a phage-displayed random peptide library reveals mimotopes of chemokine receptor CCR5: implications for the tertiary structure of the receptor and for an N-terminal binding site for HIV-1 gp120.
The chemokine receptor CCR5 contains seven transmembrane-spanning domains. It binds chemokines and acts as co-receptor for macrophage (m)-tropic (or R5) strains of HIV-1. Monoclonal antibodies (mAb) to CCR5, 3A9 and 5C7, were used for biopanning a nonapeptide cysteine (C)-constrained phage-displayed random peptide library to ascertain contact residues and define tertiary structures of possible epitopes on CCR5. Reactivity of antibodies with phagotopes was established by enzyme-linked immunosorbent assay (ELISA). mAb 3A9 identified a phagotope C-HASIYDFGS-C (3A9 / 1), and 5C7 most frequently identified C-PHWLRDLRV-C (5C7 / 1). Corresponding peptides were synthesized. Phagotopes and synthetic peptides reacted in ELISA with corresponding antibodies and synthetic peptides inhibited antibody binding to the phagotopes. Reactivity by immunofluorescence of 3A9 with CCR5 was strongly inhibited by the corresponding peptide. Both mAb 3A9 and 5C7 reacted similarly with phagotopes and the corresponding peptide selected by the alternative mAb. The sequences of peptide inserts of phagotopes could be aligned as mimotopes of the sequence of CCR5. For phage 3A9 / 1, the motif SIYD aligned to residues at the N terminus and FG to residues on the first extracellular loop; for 5C7 / 1, residues at the N terminus, first extracellular loop, and possibly the third extracellular loop could be aligned and so would contribute to the mimotope. The synthetic peptides corresponding to the isolated phagotopes showed a CD4-dependent reactivity with gp120 of a primary, m-tropic HIV-1 isolate. Thus reactivity of antibodies raised to CCR5 against phage-displayed peptides defined mimotopes that reflect binding sites for these antibodies and reveal a part of the gp120 binding sites on CCR5.


XRCC7 rs#7003908 Polymorphism and Helicobacter pylori Infection-Related Gastric Antrum Adenocarcinoma.
The X-ray repair cross-complementing group 7 (XRCC7) plays a key role in DNA repair that protects against genetic instability and carcinogenesis. To determine whether XRCC7 rs#7003908 polymorphism (XRCC7P) is associated with Helicobacter pylori (H. pylori) infection-related gastric antrum adenocarcinoma (GAA) risk, we conducted a hospital-based case-control study, including 642 patients with pathologically confirmed GAA and 927 individually matched controls without any evidence of tumours or precancerous lesions, among Guangxi population. Increased risks of GAA were observed for individuals with cagA positive (odds ratio (OR) 6.38; 95% confidence interval (CI) 5.03-8.09). We also found that these individuals with the genotypes of XRCC7 rs#7003908 G alleles (XRCC7-TG or -GG) featured increasing risk of GAA (ORs 2.80 and 5.13, resp.), compared with the homozygote of XRCC7 rs#7003908 T alleles (XRCC7-TT). GAA risk, moreover, did appear to differ more significantly among individuals featuring cagA-positive status, whose adjusted ORs (95% CIs) were 15.74 (10.89-22.77) for XRCC7-TG and 38.49 (22.82-64.93) for XRCC7-GG, respectively. Additionally, this polymorphism multiplicatively interacted with XRCC3 codon 241 polymorphism with respect to HCC risk (ORinteraction = 1.49). These results suggest that XRCC7P may be associated with the risk of Guangxiese GAA related to cagA.