Identification and hydrogenation of C2 on Pt(111).
Reflection absorption infrared spectroscopy (RAIRS) and temperature-programmed desorption (TPD) were used to identify the molecular species formed upon the reaction of hydrogen with surface carbon that is deposited by exposing acetylene to a Pt(111) surface held at 750 K. At this temperature, the acetylene is completely dehydrogenated and all hydrogen is desorbed from the surface. Upon subsequent hydrogen exposure at 85 K followed by sequential annealing to higher temperatures, ethylidyne (CCH3), ethynyl (CCH), and methylidyne (CH) are formed. The observation of these species indicates that carbon atoms and C2 molecules exist as stable species on the surface over a wide range of temperatures. Through a combination of RAIRS intensities, hydrogen TPD peak areas, and Auger electron spectroscopy, quantitative estimates of the coverages of the various species were obtained. It was found that 79% of the acetylene-derived carbon was in the form of C2 molecules, with the remainder in the form of carbon atoms. Essentially all of the acetylene-derived carbon could be hydrogenated. In contrast, 85% of an equivalent coverage of carbon deposited by ethylene exposure at 750 K was found to be inert toward hydrogenation.


Detecting inaudible vocal organ changes through glottal inverse filtering.
The aim of this study was to investigate if there were objective quantities extracted from the speech pressure waveforms that underlay inaudible changes in the symptoms of the vocal organ. This was done through analyzing 180 voice samples obtained from nine subjects (five females and four males) before and after exposure to a placebo substance (lactose) and an organic dust substance. Acoustical analysis of the voice samples was achieved by using glottal inverse filtering. Results showed that the values of primary open quotient and primary speed quotient changed significantly (P<0.05) as did the amplitude quotient (P<0.01). Exposure to lactose resulted in significant changes of secondary open quotient (P<0.05) but opposite to effects found for exposure to organic dust. Modeling of the vocal tract into cross-sectional planes revealed that the immediate plane above the vocal folds correlates inversely with the feeling that voice is tense, or feeling the need to make an effort when speaking in addition having a feeling of shortness of breath or the need to gasp for air. Such results may point to acoustically detected subclinical changes in the vocal organ that the subject him/herself feels while they remain perceptually undetected by others.


Singer's dystonia: first report of a variant of spasmodic dysphonia.
We discuss the phonatory characteristics of a previously undescribed focal laryngeal dystonia present in the singing voice. We performed a retrospective chart review of 5 patients with singer's dystonia at a neurolaryngology referral center. Four patients reviewed demonstrated phonatory characteristics consistent with adductor spasmodic dysphonia present in their singing voice. One patient demonstrated abductor spasmodic dysphonia in the singing voice. Each patient initially exhibited normal connected speech in conversational voicing. The treatment protocol and outcome are discussed, including the use of botulinum toxin. Singer's dystonia is a previously undescribed neurologic disorder that should be understood by those who treat voice performers and voice disorders.


A novel treatment of central serous chorioretinopathy with topical anti-inflammatory therapy.
A 45-year-old Caucasian female with diagnosis of central serous chorioretinopathy (CSCR) did not improve on conventional observational approach. She was not willing to proceed with photocoagulation or photodynamic therapy. An unconventional approach of topical anti-inflammatory (ketorolac, dexamethasone and hydrocortisone) preparation was prescribed. The course of her CSCR responded well on this unconventional treatment, but relapsed on cessation or tapering of treatment. After 18 weeks of treatment with a gradual taper, her condition resolved. The present case highlights an alternative but unconventional treatment of CSCR with prolonged use of anti-inflammatories.


Partial purification and characterization of a pp60v-src-related tyrosine kinase from bovine brain.
We have identified and substantially purified a tyrosine protein kinase from normal bovine brain that is immunologically related to the product of the Rous sarcoma virus oncogene (pp60v-src). The enzyme, a 61-kDa protein (p61), is solubilized with detergent from bovine cerebral cortical membranes and purified by column chromatography. In the purest preparations, this protein is phosphorylated only on tyrosine, but it can also be a substrate for serine- and threonine-specific protein kinases. The p61 protein phosphorylates the heavy chain of immunoglobulins from rabbits bearing Rous sarcoma virus-induced tumors (TBR IgG) but not normal IgG. TBR IgG precipitates the 61-kDa phosphoprotein and protein kinase activity from purified preparations. The activity of the purified brain tyrosine kinase is 10 times higher in the presence of 7-10 mM Mn2+ and 6 mM Mg2+ than it is with 6 mM Mg2+ alone. With Mn2+, the p61 enzyme has a Km for ATP of 2 microM. All preparations of p61 also contain a 64-kDa protein (p64) that is phosphorylated on tyrosine. Measurement of the Stokes radius of p61 and p64 by gel filtration shows that they are not physically associated in buffer containing the nonionic detergent Lubrol 12A9. The p64 protein is not precipitated by TBR IgG. We do not know whether p64 is only a substrate for the p61 tyrosine kinase or is itself a kinase.


The optical trapping dumbbell assay for nonprocessive motors or motors that turn around filaments.
In vitro motility assays enabled the analysis of coupling between ATP hydrolysis and movement of myosin along actin filaments or kinesin along microtubules. Single-molecule assays using laser trapping have been used to obtain more detailed information about kinesins, myosins, and processive DNA enzymes. The combination of in vitro motility assays with laser-trap measurements has revealed detailed dynamic structural changes associated with the ATPase cycle. This protocol describes the preparation of biotin-actin filaments and coverslips coated with polystyrene beads. These are then used in optical trapping dumbbell assays to study interactions between motors and filaments.


Disease-specific, patient-assessed measures of health outcome in ankylosing spondylitis: reliability, validity and responsiveness.
To assess the acceptability and measurement properties of four ankylosing spondylitis (AS)-specific, patient-assessed measures of health outcome: AS Quality of Life Questionnaire (ASQoL), Bath AS Disease Activity Index (BASDAI), the Body Chart and the Revised Leeds Disability Questionnaire (RLDQ). Instruments were administered by means of a self-completed questionnaire to patients recruited from across the United Kingdom (UK). Instruments were assessed for data quality and scaling assumptions. Where appropriate, dimensionality was assessed using principle component analysis (PCA). Internal consistency reliability was tested using Cronbach's alpha. Test-retest reliability was assessed in those patients reporting no change in AS-specific health at 2 weeks. The convergent validity of the instruments was assessed and scores were correlated with responses to the health transition questions. Responsiveness was assessed for patients reporting change in health at 6 months. The BASDAI and Body Chart have low self-completion rates. Item responses for the RLDQ were skewed towards higher levels of functional ability. PCA supported instrument unidimensionality. Cronbach's alpha ranged from 0.87 (BASDAI) to 0.93 (RLDQ). Test-retest reliability estimates support the use of the ASQoL and RLDQ in individual evaluation (>0.90). Correlations between instruments were in the hypothesized direction; the largest was between the ASQoL and BASDAI (0.79). The BASDAI had the strongest linear relationship, with responses to both specific and general health transition questions (P<0.01). With the exception of the Body Chart, instruments had a stronger relationship with general health transition. The BASDAI was the most responsive instrument. The Body Chart and RLDQ had low levels of responsiveness. The instruments have undergone a comprehensive comparative evaluation to assess the measurement properties required for patient-assessed measures of health outcome. Adequate levels of reliability and validity were found for all instruments. The BASDAI and the ASQoL were the most responsive to self-perceived change in health, but the BASDAI had low levels of self-completion.


Application of LCA Method for Assessment of Environmental Impacts of a Polylactide (PLA) Bottle Shaping.
In recent years, there has been a significant increase in the consumption of single-use packaging. Their material diversity is a significant barrier to recycling, causing overloading of landfills. Increasing negative environmental aspects have highlighted the need to develop solutions to achieve a relatively high efficiency of the bottle shaping process with the lowest possible energy consumption. The aim of the project is to try to describe the impact of this process on the state, transformation and development of the natural environment. The work concerns current issues of the impact of packaging on the natural environment. The main goal was to conduct a life cycle analysis (LCA) of beverage bottles made of polylactide. The functional unit comprised a total of 1,000 pieces of PLA bottles with a capacity of 1 L. The boundary of the adopted system included the steps from the delivery of the preforms to the production plant to their correct formation in the process of forming beverage bottles. Further stages of the production process were excluded from the system, such as beverage bottling, labeling, and storage and distribution. Processes related to transport and storage of raw material were also excluded. The LCA analysis was performed using the program of the Dutch company Pre Consultants called SimaPro 8.4.0. The ReCiPe 2016 method was chosen for the interpretation of the quantity of emitted substances into the natural environment. The test results were presented graphically on bar charts and subjected to verification and interpretation.


[Discordant anomaly in twin pregnancy].
The risk of fetal loss is multiplied by 4 in monochorionic pregnancies by comparison with dichorionic one. The incidence of selective growth retardation (sIUGR) is between 12.5 to 25%. This variation is explained by the mixture between pure twin-to-twin transfusion syndrome (TTTS) and pregnancies without TTTS but with a pure sIUGR. The ability to diagnose prenatally sIUGR is low; the positive predictive value is only 37% (EL4). The umbilical flow velocity waveforms with absent diastolic flow (Type II) or with diastolic intermittent flow (Type III) is clearly a strong risk factor of mortality of the IUGR and also a risk factor of leucomalacia of the bigger fetus (EL3). The observed incidence of malformations in twins is 4.05% versus 2.38% for singletons (OR=1.7 [IC 95% 1.47-1.97]). Furthermore, the rate of fetal malformations is higher in monochorionic pregnancies by comparison with dichorionic one, 6.33% versus 3.43% (OR=1.8 [IC 95% 1.3-2.5]) (EL3). In the majority of the cases, the malformation is concerning only one fetus. The most frequent malformations are those of the central nervous system by comparison with singletons, those of the urinary tract and the cardiovascular malformations. Monozygotic pregnancies are not necessarily phenotypically and genetically identical. In situation of asymmetrical malformation, it is necessary to propose fetal karyotype of the malformed fetus. In case aneuploidy of the malformed fetus, secondarily it will be necessary to explore the other apparently normal one. Uniparental disomy should be suspected in such situation (EL3). In TRAP sequence, an intensive follow up should be organised with serial measurement of the respective size of the acardiac fetus and the normal one, Doppler exploration should be done to look for early sign of cardiac decompensation (expert viewpoint). In dichorionic pregnancies, when the malformation is threatening the whole pregnancy like anencephaly, a selective feticide allow a prolongation of the pregnancy, but with a risk of fetal loss of 8% and a risk of iatrogenic prematurity of 12%. In such situation, it could be wise to evaluate the evolution or to wait until the third trimester to undergo the procedure (EL3). In monochorionic pregnancies, in the same situation of anencephalic fetus the best option is bipolar cord coagulation. The result seems to be better after 18 weeks of gestation (EL4). There is a 20% risk of premature rupture of membrane. In the up to date analysis of the literature, there is no formal indication of selective feticide expect case of TRAP sequence with cardiac decompensation of the normal fetus. The very special situation of sIUGR is the object of a randomized trial. In all cases the active participation of the patients to the therapeutic option is mandatory (expert viewpoint).


Plasma membrane rafts play a critical role in HIV-1 assembly and release.
HIV-1 particle production occurs in a series of steps promoted by the viral Gag protein. Although it is well established that assembly and release take place at the plasma membrane, the nature of membrane assembly sites remains poorly understood. We show here that Gag specifically associates with cholesterol-enriched microdomains ("rafts") at the plasma membrane. Kinetic studies demonstrate that raft association follows membrane binding, and the analysis of Gag mutants reveals that, whereas the N terminus of Gag mediates raft binding, this association is greatly enhanced by Gag-Gag interaction domains. We observe that depletion of cellular cholesterol markedly and specifically reduces HIV-1 particle production. Furthermore, treatment of virus-producing cells or virus particles with raft-disrupting agents significantly impairs virus infectivity. These results identify the association of Gag with plasma membrane rafts as an important step in HIV-1 replication. These findings may lead to novel strategies for suppressing HIV-1 replication in vivo.


Effects of Provocative Testing on Phase III Migrating Motor Complex in Children.
Antroduodenal manometry (ADM) is used to evaluate antral and small intestinal motility, with the presence of phase III migrating motor complexes (MMCs) indicating an intact enteric neuromuscular system. The lack of evidence-based or consensus-driven established norms for MMC in fasting phase and after provocative testing marks a major limitation in the interpretation of ADM studies. We aimed to determine the characteristics of MMC in fasting and post-provocative phase in children. Data from subjects ages <20 years with ADM results evaluated at neuro-gastroenterology and Motility Disorders Center, Cincinnati Children's Hospital Medical Center from January 2018 to March 2019 were analyzed. Forty-eight ADM tracings that did not demonstrate abnormal patterns were included; the mean age was 10.00 ± 5.72 years and 50% were male. Indications for ADM included: vomiting (27.1%), feeding intolerance (27.1%), abdominal pain (16.6%), nausea (14.6%), and abdominal distension (14.6%). Thirty-seven percent of subjects had enteral access for feeds. During fasting, one-third of all MMC originated in the antrum. Azithromycin-induced MMC occurred in 28% of subjects and two-thirds of these originated in the antrum with antral contractions of significantly higher frequency and amplitude compared to fasting. Octreotide significantly increased frequency, amplitude, and duration of MMC compared to fasting, with 76% originating in the antrum. Both azithromycin and octreotide induced more than one MMC in a third of subjects. We describe the characteristics of antral and small intestinal motility during fasting and after provocative testing in children. These values will help standardize our interpretation of pediatric ADM studies.


Lipopolysaccharide immune stimulation but not β-mannanase supplementation affects maintenance energy requirements in young weaned pigs.
Pathogen or diet-induced immune activation can partition energy and nutrients away from growth, but clear relationships between immune responses and the direction and magnitude of energy partitioning responses have yet to be elucidated. The objectives were to determine how β-mannanase supplementation and lipopolysaccharide (LPS) immune stimulation affect maintenance energy requirements (MEm) and to characterize immune parameters, digestibility, growth performance, and energy balance. In a randomized complete block design, 30 young weaned pigs were assigned to either the control treatment (CON; basal corn, soybean meal and soybean hulls diet), the enzyme treatment (ENZ; basal diet + 0.056% β-mannanase), or the immune system stimulation treatment (ISS; basal diet + 0.056% β-mannanase, challenged with repeated increasing doses of Escherichia coli LPS). The experiment consisted of a 10-d adaptation period, 5-d digestibility and nitrogen balance measurement, 22 h of heat production (HP) measurements, and 12 h of fasting HP measurements in indirect calorimetry chambers. The immune challenge consisted of 4 injections of either LPS (ISS) or sterile saline (CON and ENZ), one every 48 h beginning on d 10. Blood was collected pre- and post-challenge for complete blood counts with differential, haptoglobin and mannan binding lectin, 12 cytokines, and glucose and insulin concentrations. Beta-mannanase supplementation did not affect immune status, nutrient digestibility, growth performance, energy balance, or MEm. The ISS treatment induced fever, elevated proinflammatory cytokines and decreased leukocyte concentrations (P < 0.05). The ISS treatment did not impact nitrogen balance or nutrient digestibility (P > 0.10), but increased total HP (21%) and MEm (23%), resulting in decreased lipid deposition (-30%) and average daily gain (-18%) (P < 0.05). This experiment provides novel data on β-mannanase supplementation effects on immune parameters and energy balance in pigs and is the first to directly relate decreased ADG to increased MEm independent of changes in feed intake in immune challenged pigs. Immune stimulation increased energy partitioning to the immune system by 23% which limited lipid deposition and weight gain. Understanding energy and nutrient partitioning in immune-stressed pigs may provide insight into more effective feeding and management strategies.


Poor outcomes associated with antithrombotic undertreatment in patients with atrial fibrillation attending Gondar University Hospital: a retrospective cohort study.
Atrial fibrillation (AF) is a major risk factor for stroke as it increases the incidence of stroke nearly fivefold. Antithrombotic treatment is recommended for the prevention of stroke in AF patients. However, majorly due to fear of risk of bleeding, adherence to recommendations is not observed. The aim of this study was to investigate the impact of antithrombotic undertreatment, on ischemic stroke and/or all-cause mortality in patients with AF. A retrospective cohort study was conducted from January 7, 2017 to April 30 2017 using medical records of patients with AF attending Gondar University Hospital (GUH) between November 2012 and September 2016. Patients receiving appropriate antithrombotic management and those on undertreatment, were followed for development of ischemic stroke and/or all-cause mortality. Kaplan-Meier and a log-rank test was used to plot the survival analysis curve. Cox regression was used to determine the predictors of guideline-adherent antithrombotic therapy. The final analysis included 159 AF patients with a median age of 60 years. Of these, nearly two third (64.78%) of patients were receiving undertreatment for antithrombotic medications. Upon multivariate analysis, history of ischemic stroke/transient ischemic attack (TIA) was associated with lower incidence of antithrombotic undertreatment. A significant increase (HR: 8.194, 95% CI: 2.911-23.066)] in the incidence of ischemic stroke and/or all-cause mortality was observed in patients with undertreatment. Up-on multivariate analysis, only increased age was associated with a statistically significant increase incidence of ischemic stroke and/or all-cause mortality, while only history of ischemic stroke/TIA was associated with a decrease in the risk of ischemic stroke and/or all-cause mortality. Adherence to antithrombotic guideline recommendations was found to be crucial in reducing the incidence of ischemic stroke and/or all-cause mortality in patients with AF without increasing the risk of bleeding. However, undertreatment to antithrombotic medications was found to be high (64.78%) and was associated with poorer outcomes in terms of ischemic stroke and/or all-cause mortality. Impact on practice: This research highlighted the magnitude of antithrombotic undertreatment and its impact on ischemic stroke and/or all-cause mortality in patients with AF. This article has to alert prescribers to routinely evaluate AF patients' risk for ischemic stroke and provide appropriate interventions based on guideline recommendations.


Semiautomatic macroencapsulation of fresh or cryopreserved porcine hepatocytes maintain their ability for treatment of acute liver failure.
We have previously demonstrated that fresh or cryopreserved xenogeneic hepatocytes manually macroencapsulated in AN69 polymer and transplanted intraperitoneally in rats were able to improve the survival rate after 95% hepatectomy without immunosuppression. In addition, we developed a semiautomatic device where porcine hepatocytes were coextruded with AN69 hydrogel in order to macroencapsulate large amounts of cells. The purpose of the present study was to 1) test whether transplanted porcine hepatocytes macroencapsulated in this device remained functional as evaluated by their ability to prevent death from acute liver failure, and 2) compare the efficiency of cryopreserved or freshly isolated hepatocytes. Fresh or cryopreserved porcine hepatocytes were macroencapsulated in the semiautomatic device by coextrusion in AN69 polymer in 2-m minitubes containing 6 x 10(7) cells. Acute liver failure was induced in rats by two-step 95% hepatectomy. At the time of completion of liver resection, rats were either not transplanted with minitubes (control group I, n = 13), or were implanted with two minitubes containing culture medium (control group II, n = 11), hepatocytes killed by heat treatment (control group III, n = 10), coextruded fresh hepatocytes (group IV, n = 11), or coextruded cryopreserved hepatocytes (group V, n = 11), without immunosuppression. The survival rate at day 7 was between 0% and 31% in the three control groups. By contrast, coextruded fresh hepatocytes significantly improved the survival rate (group IV, 82%) as did cryopreserved cells (group V, 91% survival). In surviving rats, minitubes were explanted after 20 days; either fresh or cryopreserved hepatocytes appeared morphologically viable and their ultrastructure was preserved. Their detoxification capacities evaluated by the activity of the cyt P450 CYP3A4 were partly maintained. In conclusion, porcine hepatocytes macroencapsulated by coextrusion using a semiautomatic device and transplanted without immunosuppression were able to prevent death from acute liver failure in rats. Cryopreserved cells were as efficient as fresh hepatocytes.


Should medical research have a place in future clinical training?
To determine the attitudes of training grade (Senior House Officer - SHO, Specialist Registrar - SpR) and non-training grade doctors (both Staff Grade and senior or Consultant level) towards the place of research in the curriculum for junior doctors and also the pursuit of research by senior (but non-academic) clinicians. A survey of a range of doctors from differing grades (above) was sent to all doctors of the employing Trust (comprising most of the regional training scheme) with a number of fixed questions but also an opportunity to provide free-text responses. Percentages of the fixed responses were estimated and free-text responses were grouped into main themes and miscellaneous items. Despite much criticism of the current protected research time for higher trainees in psychiatry in the UK and the anticipated abolition of this within the new training structure after August 2007, we found surprising and strong support for structured research training, experience and the opportunity to pursue this at senior level even for non-academic clinical consultants. Urgent review of the new training grade curriculum is needed with emphasis on how to address the research opportunities for trainees and seniors without compromising clinical, teaching and managerial obligations. A better use of such opportunities was strongly supported rather than the proposed abolition, which seems to be fast approaching.


Next-generation selective estrogen receptor degraders and other novel endocrine therapies for management of metastatic hormone receptor-positive breast cancer: current and emerging role.
Endocrine therapy (ET) is a pivotal strategy to manage early- and advanced-stage estrogen receptor-positive (ER+) breast cancer. In patients with metastatic breast cancer (MBC), progression of disease inevitably occurs due to the presence of acquired or intrinsic resistance mechanisms. ET resistance can be driven by ligand-independent, ER-mediated signaling that promotes tumor proliferation in the absence of hormone, or ER-independent oncogenic signaling that circumvents endocrine regulated transcription pathways. Estrogen receptor 1 (ESR1) mutations induce constitutive ER activity and upregulate ER-dependent gene transcription, provoking resistance to estrogen deprivation and aromatase inhibitor therapy. The role ESR1 mutations play in regulating response to other therapies, such as the selective estrogen receptor degrader (SERD) fulvestrant and the available CDK4/6 inhibitors, is less clear. Novel oral SERDs and other next-generation ETs are in clinical development for ER+ breast cancer as single agents and in combination with established targeted therapies. Recent results from the phase III EMERALD trial demonstrated improved outcomes with the oral SERD elacestrant compared to standard anti-estrogen therapies in ER+ MBC after prior progression on ET, and other agents have shown promise in both the laboratory and early-phase clinical trials. In this review, we will discuss the emerging data related to oral SERDs and other novel ET in managing ER+ breast cancer. As clinical data continue to mature on these next-generation ETs, important questions will emerge related to the optimal sequence of therapeutic options and the genomic and molecular landscape of resistance to these agents.


Vortex String Formation in Black Hole Superradiance of a Dark Photon with the Higgs Mechanism.
Black hole superradiance, which only relies on gravitational interactions, can provide a powerful probe of the existence of ultralight bosons that are weakly coupled to ordinary matter. However, as a boson cloud grows through superradiance, nonlinear effects from interactions with itself or other fields may become important. As a representative example of this, we use nonlinear evolutions to study black hole superradiance of a vector boson that attains a mass, via a coupling to a complex scalar, through the Higgs mechanism. For the cases considered, we find that the superradiant instability can lead to a transient period where the scalar field reaches its symmetry restoration value, leading to the formation of closed vortex strings, the temporary disruption of the exponential growth of the cloud, and an explosive outburst of energy. After the cloud loses sufficient mass, the superradiant growth resumes, and the cycle repeats. Thus, the black hole will be spun down but, potentially, at a much lower rate compared to when nonlinear effects are unimportant and with the liberated energy going primarily into bosonic radiation instead of gravitational waves.


The role of nectar plants in severe outbreaks of armyworm Mythimna separata (Lepidoptera: Noctuidae) in China.
The period from March to mid April, when oriental armyworm Mythimna separata (Walker) moths migrate from South China to Central China over several nights, is an important window of time in annual armyworm population increase. The presence of nectar sources along the pathway of the migratory population is a prerequisite for moths to reach target habitats and lay eggs. Using flowering periods and geographic distributions, the major spring nectar plants suitable for M. separata moths were identified from among 102 species/varieties of apicultural nectar plants. The nectar plants proposed as important to M. separata include milk vetch Astragalus sinicus L., rape Brassica napa L. and six other species. Spearman's rank correlation analyses were conducted between the annual population size of M. separata and the acreages of milk vetch and rape in the daily stopover areas for migrating populations of M. separata during 1950-1979. The Spearman's coefficient between milk vetch and M. separata was 0.6259 and the correlation was highly significant (P<0.001). Further regression analysis with data from 1950-1979 and from 1980-1992 also revealed a close relationship between annual acreage of damaged crops/wheat and acreage of milk vetch. These results strongly suggest that the unprecedented enlargement in the geographic distribution of milk vetch from Central China into South China was the key factor in the frequent severe oriental armyworm outbreaks that occurred during 1966-1977. This is thought to be the first report in the world that reveals the key role of nectar sources in long distance, regional scale, migration of moths. The argument for the key role of milk vetch is supported by the simultaneous decline in the level of damage inflicted by M. separata and the acreage of milk vetch after 1980.


Femoral hernia in the era of TAVI - a potential obstacle for transfemoral approach: a case report and literature review.
Transcatheter aortic valve implantation (TAVI) via total percutaneous transfemoral approach is an increasingly common technique for aortic stenosis treatment. It is primarily indicated in elderly with serious comorbidities. The epidemiology of these patients tends to overlap with the incidence of femoral hernia (FH). The appearance of hernia sac at the approach site and insufficient preoperational examination can lead to serious complications. We present the first-ever reported case of subsequent femoral hernia repair during transfemoral TAVI. This report presents a case of FH/TAVI coincidence and literature review of its epidemiology. Literature review was performed to analyze similarities of femoral hernia and TAVI. The case describes an 84-year old female referred for elective TAVI. Intraoperation incarcerated femoral hernia was noticed and directly repaired. Further TAVI steps were performed on regular basis. A 2-year follow-up reported no local and general complications related to procedures. Unsuspected femoral hernia found subsequently with transfemoral TAVI may become a growing problem. The number of TAVI performed rises with indications expansion. Femoral hernia repairs constitute from 2 to 4% of all groin hernia. Both TAVI and FH are connected with elderly. Despite the fact of low FH incidence, growing number of TAVI performed and ageing of population, corresponds with higher possibility of complications. Most of these complications may end up fatal as they would involve high-risk patients. Insufficient attention is paid by cardiologists to the possible hernia appearance in the access site as this issue has been hardly ever presented in literature. Concomitant FH in TAVI patients should always be excluded in order to avoid serious complications. The case we report presents a successful subsequent FH repair during TAVI procedure. Further studies have to be conducted to provide data on how such problems ought to be managed.


Insulin-degrading enzyme: structure-function relationship and its possible roles in health and disease.
Insulin-degrading enzyme (IDE) or insulysin is a highly conserved Zn(2+) -dependent endopeptidase with an "inverted" HxxEH motif. In vivo, IDE contributes to regulate the steady state levels of peripheral insulin and cerebral amyloid beta peptide (Abeta) of Alzheimer's disease. In vitro, substrates of IDE include a broad spectrum of peptides with relevant physiological functions such as atrial natriuretic factor, insulin-like growth factor-II, transforming growth factor-alpha, beta-endorphin, amylin or glucagon. The recently solved crystal structures of an inactive IDE mutant bound to four different substrates indicate, in accordance with previous compelling biochemical data, that peptide backbone conformation and size are major determinants of IDE recognition and substrate selectivity. IDE-N and IDE-C halves contribute to substrate binding and may rotate away from each other leading to open and closed conformers that permit or preclude the entry of substrates. Noteworthy, stabilization of substrate beta strands in their IDE-bound form may explain the preference of IDE for peptides with a high tendency to self-assembly as amyloid fibrils. These structural requirements may underlie the capability of some amyloid peptides of forming extremely stable complexes with IDE and raise the possibility of a dead-end chaperone-like function of IDE independent of catalysis. Furthermore, the recent recognition of IDE as a varicella zoster virus receptor and its putative involvement in muscle cell differentiation, steroid receptor signaling or proteasome modulation suggest that IDE is a multi-functional protein with broad and relevant roles in several basic cellular processes. Accordingly, IDE functions, regulation or trafficking may partake in the molecular pathogenesis of major human diseases and become potential targets for therapeutic intervention.


Thermodynamics of water entry in hydrophobic channels of carbon nanotubes.
Experiments and computer simulations demonstrate that water spontaneously fills the hydrophobic cavity of a carbon nanotube. To gain a quantitative thermodynamic understanding of this phenomenon, we use the recently developed two phase thermodynamics method to compute translational and rotational entropies of confined water molecules inside single-walled carbon nanotubes and show that the increase in energy of a water molecule inside the nanotube is compensated by the gain in its rotational entropy. The confined water is in equilibrium with the bulk water and the Helmholtz free energy per water molecule of confined water is the same as that in the bulk within the accuracy of the simulation results. A comparison of translational and rotational spectra of water molecules confined in carbon nanotubes with that of bulk water shows significant shifts in the positions of the spectral peaks that are directly related to the tube radius.


Implication of HLA-C and KIR alleles in human papillomavirus infection and associated cervical lesions.
Human papillomavirus (HPV) regulation of host immune response leads to cervical lesions. In particular, natural killer (NK) cells are crucial for HPV control. Since specific HLA-I/KIR interactions modify NK cell activation, we analyzed HLA-C and KIR alleles in HPV infection and lesion development in 150 controls, 33 condyloma acuminatum, and 111 invasive cervical cancer (ICC) patients. We showed an increase in HLA-C1/KIR2DL2 and HLA-C1/KIR2DL3 pairs in HPV high-risk infected patients (OR 3.05, 3.24) with ICC (OR 1.33, 3.68). These data suggest HLA-C and KIR typing as risk marker for HPV infection and lesion evolution.


Concurrent and construct validity of Mediterranean diet scores as assessed by an FFQ.
The aim of the present study was to assess the concurrent and construct validity of two diet-quality indices, a modified Mediterranean diet score (mMDS) and a Mediterranean-like diet score (MLDS) additionally incorporating unhealthy food choices, as determined by an FFQ. A validation study assessing FFQ intake estimates compared with ten or more unannounced 24 h recalls. Pearson's correlation coefficients, intraclass correlation coefficients (ICC), Bland-Altman plots and the limits of agreement method were used to assess the between-method agreement of scores. Construct validity was shown using associations between nutrient intakes derived from multiple 24 h recalls and the mMDS and MLDS derived from the FFQ. Gerona, Spain. A total of 107 consecutively selected participants from a population-based cross-sectional survey. Pearson's correlations for the energy-adjusted mMDS and MLDS compared with multiple recalls were 0·48 and 0·62, respectively. The average FFQ energy-adjusted mMDS and MLDS were 102 % and 98 % of the recall-based mMDS and MLDS estimates, respectively. The FFQ under- and overestimated dietary recall estimates of the energy-adjusted MLDS by 28 % and 25 %, respectively, with slightly wider boundaries for the mMDS (31 % and 34 %). The ICC, which assesses absolute agreement, was similar to Pearson's correlations (mMDS = 0·48 and MLDS = 0·61). The mean differences between methods were similar across the range of average ratings for both scores, indicating the absence of bias. The FFQ-derived mMDS and MLDS correlated in the anticipated directions with intakes of eleven (73·3 %) and thirteen of fifteen nutrients (86·7 %), respectively. The FFQ provides valid estimates of diet quality as assessed by the mMDS and MLDS.


The normal dimensions of the sella turcica in Jordanians: a study on lateral cephalograms.
The sella turcica is an important anatomic and radiologic entity. The dimensions of the sella turcica vary greatly in normal individuals and are influenced by genetic and local factors. The main objective of this study is to build up a normative database of the dimensions of the sella turcica in the Jordanian population. For this purpose 509 computed cephalograms of 252 male and 257 female healthy Jordanians aged 10-40 years were collected and divided into two adolescent and adult age-groups for both genders. Viewbox 3 software was used to determine linear dimensions and area of the sella turcica. Our results showed that the overall values for width, length, height, area, and aperture (interclinoid distance) were 8.72, 7.68, 6.25, 40.80, 3.92, and 8.67, 7.42, 6.38, 41.26, 3.68 mm (mm2) for males and females, respectively. Significant differences were found between adult male group on one hand and adolescent female group and adult female group on the other hand. Between age categories and within male and female groups, sella parameters were significantly different between adolescent and adult age-groups. Our data clearly confirm the classical notion of general trend of increase in parameters with age, irrespective of gender, with the area scoring the highest increase, and the height in females and length in males contributing most obviously to this trend. The aperture appears to decrease in females while it increases in males as adulthood is reached. This seems to reflect differential growth of the pituitary gland under neurohormonal effects.


Using gene expression profiles from peripheral blood to identify asymptomatic responses to acute respiratory viral infections.
A recent study reported that gene expression profiles from peripheral blood samples of healthy subjects prior to viral inoculation were indistinguishable from profiles of subjects who received viral challenge but remained asymptomatic and uninfected. If true, this implies that the host immune response does not have a molecular signature. Given the high sensitivity of microarray technology, we were intrigued by this result and hypothesize that it was an artifact of data analysis. Using acute respiratory viral challenge microarray data, we developed a molecular signature that for the first time allowed for an accurate differentiation between uninfected subjects prior to viral inoculation and subjects who remained asymptomatic after the viral challenge. Our findings suggest that molecular signatures can be used to characterize immune responses to viruses and may improve our understanding of susceptibility to viral infection with possible implications for vaccine development.


Bradycardia in a patient taking black cohosh.
Cimicifuga racemosa, better known as black cohosh, has been widely used in Western cultures as a herbal treatment for relieving symptoms of menopause. It has previously been linked to cases of liver toxicity. We report a case of reversible complete heart block in a woman who had recently begun taking a herbal supplement containing black cohosh. We review the known side effect profile of black cohosh and its relationship to our case.


Roles of reproductive corticotropin-releasing hormone.
Corticotropin-releasing hormone (CRH), the principal regulator of the hypothalamic-pituitary-adrenal axis, as well as its receptors, have been identified in most female reproductive tissues, including the uterus, placenta, and ovary. Endometrial CRH may participate in decidualization, implantation, and early maternal tolerance; placental CRH may participate in the physiology of pregnancy and the onset of parturition, and ovarian CRH may participate in follicular maturation, ovulation, and luteolysis. The hypercortisolism of the latter half of pregnancy can be explained by increased levels of placental CRH in plasma. This hypercortisolism is followed by a transient suppression of hypothalamic CRH secretion in the postpartum period, which may explain the blues or depression and autoimmune phenomena frequently observed during this period.


Conceptions and misconceptions of the menstrual cycle.
Eighty college women were queried about their knowledge of three aspects of the menstrual cycle (menstruation, ovulation, and menopause). Questions concerned the biology of each event and the physical, emotional, and cognitive changes believed to be associated with them. Reasoning from the biases and limitations in the scientific and popular literature, it was predicted that: (1) women would be relatively uninformed about the menstrual cycle, but more informed about menstruation than about ovulation or menopause, and (2) negatively valued changes would be described more frequently than positively valued ones. Results indicated that basic knowledge of the menstrual cycle, even among well-educated women, is at times incorrect, generally incomplete, and negatively biased. These findings confirm the need for a more comprehensive approach to menstrual education that speaks both to the biology of the menstrual cycle and to norms and variability of associated physical and behavioral changes.


[Malignant pheochromocytoma responsive to multimodal therapy: a case report].
A 62-year-old man underwent right adrenalectomy for pheochromocytoma in May 1987. He was referred to our department for a right renal tumor suggested by ultrasound sonography in December 2000. Computated tomography and MRI showed a 10 cm mass arising from the upper pole of the right kidney. 131I-MIBG scintigram showed strong radio isotope accumulation consistent with the tumor. Right nephrectomy and subsegmental hepatectomy were performed. Histological findings led to the diagnosis of malignant pheochromocytoma. In February 2001, he complained of paraplasia due to Th2 bone metastasis. Radiation and CVD (cyclophosphamide, vincristine, dacarbazine) chemotherapy resulted in tumor regression and marked improvement of clinical symptoms.


Effects of corn grain conservation method on feeding behavior and productivity of lactating dairy cows at two dietary starch concentrations.
Effects of conservation method of corn grain and dietary starch concentration on dry matter intake (DMI) and productivity of lactating dairy cows were evaluated. Eight ruminally and duodenally cannulated Holstein cows (55 +/- 15.9 d in milk; mean +/- SD) were used in a duplicated 4 x 4 Latin square design with a 2 x 2 factorial arrangement of treatments. Experimental diets contained either ground high-moisture corn (HM) or dry ground corn (DG) at two dietary starch concentrations (32 vs 21%). Mean particle size and dry matter (DM) concentration of corn grain were 1863 pm and 63.2%, and 885 microm and 89.7%, for HM and DG, respectively. DMI was lower for HM compared to DG treatment in high-starch diets (20.8 vs 22.5 kg/d), but similar for the HM and DG treatments in low-starch diets (19.7 vs 19.6 kg/d). This reduction in DMI is attributed to smaller meal size for HM compared to DG in high-starch diets (1.9 vs 2.3 kg of DM for high-starch diets; 2.1 vs 2.0 kg of DM for low-starch diets). Faster starch fermentation for HM in high-starch diets might result in satiety with smaller meal size. Milk yield was greater when cows were fed high-starch diets compared to low-starch diets (38.6 vs 33.9 kg/d) regardless of corn grain treatment. High-starch diets increased solids-corrected milk yield by 3.3 kg (35.2 vs 31.9 kg/d) compared to low-starch diets for cows fed DG, but did not increase for cows fed HM. This was because of a lower milk fat concentration for cows fed HM in high-starch diets. Reducing ruminal starch fermentation by substituting DG for HM can increase the productivity of lactating cows fed high-starch diets.


Identification of iron-regulated genes of Helicobacter pylori by a modified fur titration assay (FURTA-Hp).
The Escherichia coli-based Fur titration assay (FURTA), although a powerful tool for identification of genes regulated by the ferric uptake regulator (Fur), was unsuccessful for the gastric pathogen Helicobacter pylori. The FURTA was modified by construction of an E. coli indicator strain producing H. pylori Fur only. The promoter regions of the ferric citrate receptor homolog fecA2 and the riboflavin synthesis gene ribBA were both positive in the modified FURTA, but negative in the original FURTA. Transcription of fecA2 and ribBA was demonstrated to be iron-repressed in H. pylori. This type of modification should allow FURTA analysis for bacteria with Fur binding sequences poorly recognized by E. coli Fur.


Characterization of aerosols from hemp-derived pre-roll joints.
Availability and consumer use of hemp products is rapidly increasing, but little work has been done to assess aerosol emissions of hemp pre-rolls. The objective of this research was to characterize the aerosol of pre-rolled joints from hemp material enriched for production of cannabigerol (CBG) that were smoked on a test system mimicking human use patterns. Aerosol emissions were collected and analyzed using glass microfiber filters and charcoal cartridges. The aerosol was screened for nine phytocannabinoids and 19 terpenes. Three phytocannabinoids (CBG, cannabichromene (CBC), and delta-9-tetrahydrocannabinol (THC)) were detected and quantified at a mean (SD) concentration of 19.4 (4.7), 0.48 (0.01), and 0.40 (0.04) mg per pre-roll, respectively. Five terpenes ((-)-α-bisabolol, (-)-guaiol, β-caryophyllene, nerolidol, and α-humulene) were detected and quantified at an average concentration of 352.7 (112.0), 194.3 (66.4), 106.0 (50.4), 28.3 (9.3), and 27.7 (11.2) µg per pre-roll, respectively. Particle size distribution testing via aerodynamic particle sizer and inertial impactor showed that average size of emitted aerosols was 0.77 (0.0) and 0.54 (0.1) µm, respectively. This study describes methodology for characterization of cannabinoid and terpene dose in emitted aerosols and aerosolization efficiency from hemp pre-rolls. It also presents these data for one of the marketed products.


A Modified Genetic Algorithm With New Encoding and Decoding Methods for Integrated Process Planning and Scheduling Problem.
Due to the complementarity of the process planning and shop scheduling, their integration can greatly facilitate the development of the intelligent manufacturing system. In the last decade, the integrated process planning and scheduling (IPPS) problem has become a research hotspot in the manufacturing system area. It is an NP-hard problem and is more complicated than the job shop scheduling problem. Although some progress has been obtained in the IPPS field, there are still many unsolved open problems. In this article, the novel integrated encoding and decoding methods are proposed by considering the OR-node of the process network graph. Moreover, a modified genetic algorithm (MGA) is designed based on the proposed coding methods. The process planning and the scheduling parts can be represented simultaneously in one individual. As for the precedence constraints between operations, the specifically designed operators are able to guarantee the feasibility of the operation sequence during the searching procedure. Then, the superiority of MGA is verified by updating nine new records on 37 well-known open problems, four of them reach their lower bounds. In addition, the proposed algorithm is also tested on a real-world case from a nonstandard equipment workshop in a Chinese machine tool company, which produces a common module of a packaging machine. The results show that the proposed MGA can solve the real-world case better than the comparative algorithms.


Tryptophan-Rich and Proline-Rich Antimicrobial Peptides.
Due to the increasing emergence of drug-resistant pathogenic microorganisms, there is a world-wide quest to develop new-generation antibiotics. Antimicrobial peptides (AMPs) are small peptides with a broad spectrum of antibiotic activities against bacteria, fungi, protozoa, viruses and sometimes exhibit cytotoxic activity toward cancer cells. As a part of the native host defense system, most AMPs target the membrane integrity of the microorganism, leading to cell death by lysis. These membrane lytic effects are often toxic to mammalian cells and restrict their systemic application. However, AMPs containing predominantly either tryptophan or proline can kill microorganisms by targeting intracellular pathways and are therefore a promising source of next-generation antibiotics. A minimum length of six amino acids is required for high antimicrobial activity in tryptophan-rich AMPs and the position of these residues also affects their antimicrobial activity. The aromatic side chain of tryptophan is able to rapidly form hydrogen bonds with membrane bilayer components. Proline-rich AMPs interact with the 70S ribosome and disrupt protein synthesis. In addition, they can also target the heat shock protein in target pathogens, and consequently lead to protein misfolding. In this review, we will focus on describing the structures, sources, and mechanisms of action of the aforementioned AMPs.


Association between the M235T polymorphism of the AGT gene and cytokines in patients with hypertension.
The aim of the present study was to explore the association between the M235T polymorphism of the angiotensinogen (AGT) gene and cytokines in patients with essential hypertension (EH). A total of 300 patients with EH and an age-matched control group of 150 individuals without EH, secondary hypertension, myocardial infarction and diabetes were enrolled in this study. Polymerase chain reaction combined with restriction fragment length polymorphism (PCR-RFLP) was used to detect variation in the target genotype, and enzyme-linked immunosorbant assay (ELISA) was used to detect the cytokine [interleukin (IL)-1, IL-6 and tumor necrosis factor-α (TNF-α)] concentrations. The AGT gene 235T allele and 235TT genotype frequencies in hypertensive patients were slightly higher than those in the controls. Furthermore, in the hypertensive subjects with the AGT gene 235T allele, the concentrations of IL-1 and TNF-α were significant higher than those in the controls. The results from our study suggest that the higher AGT gene TT genotype and 235T allele frequencies may be risk factors for hypertension. High frequencies of the AGT gene 235T allele and high cytokine concentrations (IL-1 and TNF-α) may promote the transcription and expression of AGT, particularly in hypertensive patients with the 235TT genotype.


Innate memory phenotype CD4+ T cells play a role in early protection against infection by Listeria monocytogenes in a CD30L-dependent manner.
CD30 ligand (CD30L, CD153) is a type II membrane-associated glycoprotein belonging to the tumor necrosis factor family. It is shown here that CD30L knock out (KO) mice are highly susceptible to primary infection with Listeria monocytogenes as assessed by the survival rate. There were significantly more bacteria on day 3 after infection in the peritoneal cavity, spleen and liver of CD30LKO mice than in wild type (WT) mice. The innate function of memory phenotype (MP) CD44+ CD4+ T cells for interferon-gamma production was significantly lower in CD30LKO mice than in WT mice in response to interleukin (IL)-12 and IL-15 in vitro. Depletion of CD4+ T cells by in vivo administration of anti-CD4 mAb at an early stage after infection hampered protection against Listeria. Furthermore, in vivo administration of agonistic anti-CD30 mAb restored protection against Listeria in CD30LKO mice, whereas treatment with soluble mCD30-Ig hampered protection in WT mice. Taken together, it appears that CD30L/CD30 signaling plays an important role in innate MPCD4+ T cell-mediated protection against infection with L. monocytogenes.


The rho guanosine 5'-triphosphatase, cell division cycle 42, is required for insulin-induced actin remodeling and glucagon-like peptide-1 secretion in the intestinal endocrine L cell.
Rho GTPases, such as cell division cycle 42 (Cdc42) and ras-related C3 botulinum toxin substrate 1 (Rac1), have been identified as regulators of F-actin dynamics and hormone release from endocrine cells; however, their role in secretion of the incretin hormone, glucagon-like peptide-1 (GLP-1), from the enteroendocrine L cell is unknown. Insulin induced a 1.4-fold increase in L cell GLP-1 release; however, secretion was potentiated to 2.1-fold in the presence of the F-actin depolymerizing agent, latrunculin B, suggesting that F-actin functions as a permissive barrier. In murine GLUTag L cells, insulin stimulated F-actin depolymerization and Cdc42 activation simultaneously, and these events occurred prior to detectable increases in insulin-induced GLP-1 release. After insulin treatment, Cdc42-dependent p21-activated kinase-1 (PAK1) activation was also detected, and transfection of small-interfering RNA against Cdc42 or of dominant-negative Cdc42(T17N) impaired insulin-stimulated PAK1 activation, actin remodeling, and GLP-1 secretion. Overexpression of kinase-dead PAK1(K299R) or PAK1 small interfering RNA similarly attenuated insulin-induced GLP-1 secretion. Knockdown or inhibition of Cdc42 and PAK1 activities also prevented activation of MAPK/ERK (MEK)-1/2-ERK1/2 by insulin, which was previously identified as a critical pathway for insulin-regulated GLP-1 release. Taken together, these data identify a novel signaling pathway in the endocrine L cell, whereby Cdc42 regulates actin remodeling, activation of the cannonical 1/2-ERK1/2 pathway and PAK1, and GLP-1 secretion in response to insulin.


Prospects of therapy for infections with human T-lymphotropic virus type III.
Human T-lymphotropic virus type III is susceptible to attack at various sites during its replicative cycle. Inhibitors of reverse transcriptase activity, including suramin, antimoniotungstate (HPA-23), and trisodium phosphonoformate, have shown in-vitro activity against the virus in early clinical trials. Other significant antiviral agents are recombinant interferon alpha-A, ribavirin, and ansamycin. Double-blind, placebo-controlled clinical trials of interferon alpha, which inhibits viral replication at easily achievable serum levels, are underway. The development of optimal therapeutic regimens will require carefully controlled, multicenter collaborative trials with standardized criteria for evaluating responses. Prolonged treatment with combinations of antiviral and immunomodulating agents may be necessary for control of HTLV-III replication and for effective treatment of the acquired immunodeficiency syndrome.


Substrate specificity for catalysis of phosphodiester cleavage by a dinuclear Zn(II) complex.
The 2.4 kcal mol(-1) greater stabilization of the transition state for cleavage of the minimal substrate HpPNP compared to the nucleoside substrate UpPNP by the efficient dinuclear metal ion catalyst Zn2(L2O) provides evidence that access to the cationic core of Zn2(L2O) is sterically blocked for the bulkier nucleoside substrates, a flaw that will need to be dealt with in later generations of metal ion catalysts of RNA cleavage.


ING-1, a monoclonal antibody targeting Ep-CAM in patients with advanced adenocarcinomas.
To determine the feasibility of administration, safety, toxicity, immunogenicity, pharmacokinetics, maximum tolerated dose, and biodistribution of ING-1, a high-affinity, Human-Engineered monoclonal antibody (heMAb) to the Mr 40,000 epithelial cell adhesion molecule Ep-CAM, in patients with advanced adenocarcinomas. ING-1 was initially administered to patients as a 1-hour intravenous infusion every 3 weeks. Toxicity and pharmacokinetic data led to the evaluation of a weekly schedule. The distribution of iodine-131 (131I)-labeled ING-1 was studied. Twenty-five patients received 82 courses of ING-1. Minimal toxicity was initially observed at the 0.03-, 0.10-, and 0.30-mg/kg dose levels. A patient dosed at 1.0 mg/kg developed acute pancreatitis with severe abdominal pain, nausea, and vomiting. A patient dosed at 0.3 mg/kg had an asymptomatic amylase and lipase elevation to 502 units/L and 1,627 units/L, respectively. Both patients made uncomplicated recoveries. No other dose-limiting toxicities were observed. Regardless of dose, the volume of distribution (mean +/- SEM) was 46.6 +/- 1.6 mL/kg. ING-1 clearance decreased with increasing dose. To minimize toxicity and increase dose intensity, we then administered ING-1 weekly. No significant toxicity was observed in 7 patients dosed at 0.1 mg/kg. Studies of 131I-labeled ING-1 biodistribution showed radiolocalization to colorectal and prostate cancers. A patient with colorectal cancer had an 80% decrement in the levels of carcinoembryonic antigen. The recommended dose for ING-1 is 0.10 mg/kg by intravenous infusion weekly. The absence of severe toxicity at this dose, low immunogenicity, and preliminary evidence of ING-1 tumor localization and antitumor efficacy support the further clinical development of this antibody to treat Ep-CAM-positive malignant diseases.


TlyA protein of Mycobacterium leprae: a probable bio-marker of active infection.
The extent of pathogenicity of the mycobacterial infections depends on virulence factors that mediate survival inside macrophages. Virulence factors are generally believed to be specific for pathogenic species and mutated/non-functional in nonpathogenic strains. Mycobacterial TlyA can modulate the phagolysosome maturation pathway, immediately after entry into macrophages. Over-expression of open reading frame (ORF) ML1358 (tlyA) in tissues of leprosy patients by partial DNA chip and real time PCR analysis during active infection attracted our interest to explore the properties of this gene at molecular and serological levels, to understand its role in the host. Molecular properties were studied by cloning and expression of the corresponding gene in pASK-iba 43(þ) expression vector in E. coli and bioinformatics tools while sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and ELISA were applied to investigate the serological significance of rTlyA protein in different clinical states of leprosy. We observed that TlyA has a close relation among mycobacteria with specific protein domains in slow growing intracellular adapted pathogenic species. The presence of trans-membrane domains indicates its association to the cell membrane. The study revealed its highly significant sero-reactivity (P value , 0·001) in borderline lepromatous (BL) patients, and those with reversal reaction (RR) and erythema nodosum leprosum (ENL). Its role in active infection, association with the cell membrane, presence in pathogenic species and high sero-reactivity, suggested the tlyA gene as a strong disease progression marker.


[The effects of an essential oil mouthrinse on oral health in the community indwelling elderly].
The purpose of this study was to investigate the effects of an essential oil mouthrinse with gingival massage on oral health in community indwelling elderly. The subjects were composed of 61 healthy elderly at a Senior Welfare Center in J city. Thirty subjects in the experimental group were given toothbrushing education ongingival massage toothbrushing with an essential oil mouthrinse for 2 weeks(4 times per day, 3 minutes per session). The 31 subjects in the control group were given toothbrushing education ongingival massage toothbrushing. The effects of the treatment were measured by salivary pH, salivary IgA level, halitosis, oral subjective symptoms, and oral self care behavior scores before, right after and 2 weeks after the experiment. Salivary pH was significantly increased(p=0.018) in the experimental group. Salivary IgA levels were not significantly different between the experimental and control groups; however, IgA levels of the experimental group were significantly increased(p=0.006) after time had passed. Halitosis was significantly decreased(p=0.002) in the experimental group. Oral subjective symptom scores were significantly decreased(p=0.000) and oral self care behavior scores were significantly increased(p=0.000) in the experimental group. Regular gingival massage toothbrushing with an essential oil mouthrinse could be an effective oral health nursing intervention for the elderly.


Prevalence of zoonotic parasites in feral cats of Central Virginia, USA.
Felis catus, the domestic cat, is the definitive host for parasites that may result in adverse health outcomes in humans. Prevalence data of zoonotic parasites in feral cats, which are free-roaming domestic cats that are born and live in the wild, are limited. The objective of this study was to assess seroprevalence of Toxoplasma gondii antibodies and copro-prevalence of potentially zoonotic parasites in feral cats and to evaluate risk factors for seropositivity and faecal excretion of parasites. In this cross-sectional survey, 275 feral cats at Trap-Neuter-Release clinics in Central Virginia were tested for parasites via faecal flotation, direct immunofluorescence assay (faeces) and modified agglutination testing (serum). Toxoplasma gondii seroprevalence was 22.35% (95% CI: 17.47-27.86). Faecal prevalence of T. gondii-like oocysts was 1.04% (95% CI: 0.13-3.71), Toxocara cati 58.85% (95% CI: 51.54-65.89), Ancylostoma spp. 18.75% (95% CI: 13.49-25.00), Giardia duodenalis 5.73% (95% CI: 2.89-10.02) and Cryptosporidium spp. 3.33% (95% CI: 1.37-7.24). Female cats were more likely than males to excrete faecal Ancylostoma spp. eggs (OR 2.88; 95% CI 1.34-6.17). Adults were more likely than immature cats to be seropositive (OR 2.10; 95% CI: 1.11-3.97) and to excrete faecal Ancylostoma spp. eggs (OR 2.57; 95% CI: 1.10-5.99). However, immature cats were more likely than adults to excrete T. cati eggs (OR 6.79; 95% CI: 3.31-13.90) and to excrete one or more potentially zoonotic species (OR 4.67; 95% CI: 2.28-9.55) in faeces. Results of this study have implications for human and animal health and highlight the importance of collaboration between public health, medical and veterinary communities in preventive efforts.


Quantitative determination of pulegone in pennyroyal oil by FT-IR spectroscopy.
Pulegone constitutes a monoterpene occurring in Mentha species and primarily in Mentha pulegium L. (pennyroyal). A major source of human exposure to pulegone is the use of pennyroyal essential oil in flavorings, confectionery and cosmetics. The rapid quantification of pulegone in hydrodistilled pennyroyal oils (which were also "spiked" to increase the validation range) by Fourier transform infrared spectroscopy (FT-IR) combined with partial least-squares (PLS) regression was evaluated, using the spectral region 1650-1260 cm(-1). Gas chromatography was applied as the reference method for pennyroyal oil samples, which ranged in pulegone content from 157 to 860 mg/mL. The two methods were subjected to statistical tests and proved equivalent in terms of accuracy and reproducibility (99% confidence level). The use of FT-IR spectroscopy could offer a viable alternative to the standard analysis procedures presently applied for quantification of valuable plant substances and could also provide the processing industry with a simple and high-throughput technique for the fast quality check of incoming raw materials such as pennyroyal oils.


Role of ZEB Family Members in Proliferation, Metastasis, and Chemoresistance of Prostate Cancer Cells: Revealing Signaling Networks.
Prostate cancer (PCa) is one of the leading causes of death worldwide. A variety of strategies, including surgery, chemotherapy, radiotherapy, and immunotherapy, are applied for PCa treatment. PCa cells are responsive towards therapy at early stages, but they can obtain resistance in the advanced stage. Furthermore, their migratory ability is high in advanced stages. It seems that genetic and epigenetic factors play an important role in this case. Zinc finger E-box-binding homeobox (ZEB) is a family of transcription with two key members, including ZEB1 and ZEB2. ZEB family members are known due to their involvement in promoting cancer metastasis via EMT induction. Recent studies have shown their role in cancer proliferation and inducing therapy resistance. In the current review, we focus on revealing the role of ZEB1 and ZEB2 in PCa. ZEB family members are able to significantly promote the proliferation and viability of cancer cells. ZEB1 and ZEB2 enhance migration and invasion of PCa cells via EMT induction. Overexpression of ZEB1 and ZEB2 is associated with a poor prognosis of PCa. ZEB1 and ZEB2 upregulation occurs during PCa progression and can provide therapy resistance to cancer cells. PRMT1, Smad2, and non-coding RNAs can function as upstream mediators of the ZEB family. Besides, Bax, Bcl-2, MRP1, Ncadherin, and E-cadherin can be considered as downstream targets of the ZEB family in PCa.


[Effect and mechanism of adipocyte co-culture on aquaporin-9 expression in HepG2 cells].
Objective: To observe the effect of differentiated mature adipocytes on hepatic steatosis and aquaporin-9 (AQP9) expressions in HepG2 cells and further explore its possible mechanism of action. Methods: Human preadipocytes were cultured and differentiated to full maturity. HepG2 cells were co-cultured with non-differentiated adipocytes and differentiated mature adipocytes for 48 h, and then labeled as control group and experimental group. Oil red O staining and intracellular triglyceride content were performed on co-cultured HepG2 cells and simultaneous changes in phosphatidylinositol 3-kinase (PI3K) - serine/threonine kinase (Akt) signaling pathway, and AQP9 mRNA and protein levels were detected. The experimental group was co-cultured with recombinant human insulin-like growth factor-I (IGF-I), with the addition of 100ng/ml PI3K-Akt pathway agonist, labeled as experimental group + IGF-I group. The activation of PI3K-Akt pathway was verified by Western blotting (WB). The expression of AQP9 was detected by RT-q PCR and WB. The recombinant lentivirus LV-AQP9 or empty-loaded virus LV-PWPI was transfected with HepG2 cells by recombinant lentiviral transfection tecnique, and labeled as HepG2-AQP9 and HepG2-PWPI. The transfection efficiency was assessed by confocal laser scanning microscopy and RT-qPCR and WB detected the change of AQP9 expression level after virus transfection. Afterwards, the stable over-expressed HepG2-AQP9 cells and the empty-loaded HepG2-PWPI cells were co-cultured with differentiated mature adipocytes for 48h, and labeled as HepG2-AQP9 co-culture group, and then intracellular triglyceride content were detected with Oil red O staining. Finally, IGF-I was added to the HepG2-AQP9 co-culture group, which was recorded as HepG2-AQP9 co-culture + IGF-I group. Intracellular triglyceride content was detected with Oil red O staining, and WB verified PI3K-Akt signaling pathway activation and changes in AQP9 mRNA and protein levels. A t-test was used to compare the two independent samples. Results: The intracellular lipid droplets and triglyceride content (0.052 ± 0.005) in the experimental group was increased significantly than the control group (0.033 ± 0.003) (t= 5.225,P= 0.006), suggesting that adipocyte co-culture had induced steatosis in HepG2 cells. RT-qPCR and WB results indicated that the expression levels of AQP9 mRNA (3.615 ± 0.330) and protein levels (0.072 ± 0.005) in the experimental group were significantly higher than the control group (t= 13.708, 11.225,P= 0.005, < 0.001). WB results showed that the expression level of phosphorylated Akt (p-Akt) protein (0.116±0.003) in the experimental group was significantly lower than the control group (0.202 ± 0.003) (t= 27.136,P< 0.001). The total Akt protein was constant, and the p-Akt/total Akt (0.182 ± 0.017)was significantly lower than the control group (0.327 ± 0.019) (t= 2.431,P= 0.001), suggesting that adipocyte co-culture had inhibited PI3K- Akt signaling pathway in HepG2 cells and up-regulated the expression level of AQP9. WB results indicated that the expression level of p-Akt protein (0.194 ± 0.021) in the experimental group + IGF-I group was significantly higher than the experimental group (0.132 ± 0.003) (t= 5.082,P= 0.007). The total Akt protein was constant, and the p-Akt/total Akt (0.281 ± 0.009) was significantly higher than the control group (0.184 ± 0.132) (t= 10.311,P< 0.001). Simultaneously, RT-qPCR and WB results indicated that the expression levels of AQP9 mRNA (0.327 ± 0.347) and protein levels (0.042 ± 0.004) in the experimental group + IGF-I group were significantly lower than the experimental group (t= 33.573, 5.598,P< 0.001, 0.005), suggesting that adipocyte co-culture had possibility to regulate the expression level of AQP9 through the PI3K-Akt pathway. Confocal laser microscopy analysis showed that the transfection efficiency was more than 90%. RT-q PCR and WB results indicated that the expression levels of AQP9 mRNA and protein levels (0.373 ± 0.221) in HepG2-AQP9 group were significantly higher than HepG2-PWPI group (t=14.953, 28.931,P= 0.002 and 0.000), suggesting that the stable overexpression of AQP9 cell line was successfully constructed. The intracellular lipid droplets and triglyceride content in HepG2-AQP9 co-culture group was significantly increased (t= 5.478, 5.369,P= 0.005) than HepG2-PWPI co-culture group and HepG2-AQP9 co-culture+ IGF-I group, suggesting that the increased expression of AQP9 had promoted HepG2 steatosis in co-cultured adipocytes. WB results showed the expression levels of p-Akt protein (0.168 ± 0.006) and p-Akt/total Akt (0.265±0.009) in HepG2-AQP9 co-culture + IGF-1 group was significantly increased (t= 16.311, 8.769,P< 0.001) than HepG2-AQP9 co-culture group, while the expression levels of AQP9 mRNA (0.327 ± 0.034) and protein (0.375 ± 0.025) was significantly decreased (t= 33.573, 9.146,P< 0.001 and 0.001). Conclusion: Adipocytes co-culture can induce steatosis in HepG2 cells, and may participate in inhibiting PI3K-Akt signaling pathway to upregulate the expression of AQP9 in steatotic HepG2 cells.


Antibiotics and nephrostomy tube care: preliminary observations. Part II. Bacteremia.
Bacteriuria occurs after long-term drainage of the kidney. This study was designed to determine if the risk of bacteremia increases at the time of tube or stent change, whether bacteremia correlates with clinical infection, and if prophylactic antibiotics are effective in the prevention of bacteremia. One hundred four tube changes in 74 patients with percutaneous nephrostomy tubes and documented positive urine cultures were studied. Patients were arbitrarily divided into groups receiving and not receiving antibiotics before nephrostomy tube change. Asymptomatic bacteremia was documented in 11 of 104 tube changes (11%). Results of five blood cultures were positive in the group receiving antibiotics, and six cases of bacteremia occurred in the group not receiving antibiotics (P = .96). Routine nephrostomy/stent change can cause frequent, asymptomatic bacteremia in patients with colonization of bacteria in the urinary tract. Antibiotic prophylaxis was unsuccessful in preventing transient bacteremia, a factor that may have implications in patients with underlying valvular heart disease and other patients at risk for bacteremia.


New insights into idiopathic infantile arterial calcinosis. Three patient reports.
We describe the occurrence of idiopathic infantile arterial calcinosis in three newborn siblings. Unusual features in this disease include ultrasonographic prenatal diagnosis in the second two siblings and ultrastructural studies of the third patient that might shed light on the pathophysiologic characteristics of this disease. Ruthenium-red staining for proteoglycans showed a clearly abnormal structure for the granules in areas of calcification. The granules appeared disorganized, with loss of their normal honeycomb interconnections. They also varied in size and density. In addition, matrix vesicles that might serve as nucleation sites for crystalline calcium phosphate were observed in zones of calcification.


Second Edition of Special Issue "Strategies and Evidence in Health Communication: Evidence and Perspectives".
The second edition of this Special Issue "Strategies and Evidence in Health Communication", published in the International Journal of Environmental Research and Public Health aims primarily to increase international literature evidence and observations in the field regarding: (i) health communication strategies and crisis communication, (ii) health education and health advocacy, and (iii) the fight against the phenomenon of Vaccine Hesitancy (VH) through training and communication activities targeting the general public and health professionals. This Special Issue builds on the premise that, despite the fact that theoretical and experimental research has contributed to an increase in knowledge and evidence about the importance of communication in healthcare, communication professionals in this field still face great challenges when trying to develop messages that effectively change the behavior of large groups of people. The need to relay fast and reliable information to the general public has therefore led public institutions to seek out new and innovative ways of transmitting health-related content. In particular, for some time now, Public Health has also been making use of the Internet and Information and Communication Technologies (ICT) to reach various population groups and achieve better health conditions for all. This practice, known as Digital Health or E-health, provides healthcare using digital tools (e.g., websites and social media networks) and easy-to-understand language. This is particularly important in the current pandemic context, where Public Health continues to face many problems and difficulties in persuading people to adhere to the guidelines issued for the containment of COVID-19, with particular reference to vaccination programs, hence the importance of acquiring and strengthening communication skills in healthcare, where correct and effective communication is immediately beneficial both to professionals and patients.


Transcriptional noise and cellular heterogeneity in mammalian macrophages.
Transcriptional noise is known to play a crucial role in heterogeneity in bacteria and yeast. Mammalian macrophages are known to exhibit cell-to-cell variation in their responses to pathogens, but the source of this heterogeneity is not known. We have developed a detailed stochastic model of gene expression that takes into account scaling effects due to cell size and genome complexity. We report the results of applying this model to simulating gene expression variability in mammalian macrophages, demonstrating a possible molecular basis for heterogeneity in macrophage signalling responses. We note that the nature of predicted transcriptional noise in macrophages is different from that in yeast and bacteria. Some molecular interactions in yeast and bacteria are thought to have evolved to minimize the effects of the high-frequency noise observed in these species. Transcriptional noise in macrophages results in slow changes to gene expression levels and would not require the type of spike-filtering circuits observed in yeast and bacteria.


Influence of subcutaneous administration of recombinant TNF-alpha on ligature-induced periodontitis in rats.
Proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) was found in inflamed periodontal tissues and many studies pointed to its significant role in development of periodontal disease. In this study, the influence of subcutaneously administered recombinant human TNF-alpha (rhTNF-alpha) on inflammatory reaction and periodontal breakdown in rats was analyzed during experimental periodontitis, induced by placing silk ligatures around the maxillary right second molar tooth. The rats were divided into two groups with five animals in each; the first group was infused subcutaneously with rhTNF-alpha via osmotic pumps for 2 weeks and the second group was infused with phosphate-buffered saline (PBS) in the same manner. Inflammatory reaction and periodontal breakdown was evaluated morphometrically on hematoxylin and eosin stained sections. Serum ionized calcium and inorganic phosphates were monitored colorimetrically. Serum calcium and phosphate levels were similar in rats receiving rhTNF-alpha and PBS. Ligation resulted in accelerated periodontal breakdown, while subcutaneous rhTNF-alpha administration by itself had no significant effect. Combined effect of subcutaneous rhTNF-alpha administration and ligation resulted in a significantly greater inflammatory reaction and periodontal breakdown then either treatment alone. We concluded that the subcutaneous administration of rhTNF-alpha accelerates the progression of experimental periodontitis in rats.


Palladium(0) versus nickel(0) catalysis in selective functional-group-tolerant sp(3)-sp(3) carbon-carbon bond formations.
We have uncovered Pd(0)-catalyzed intermolecular nonsymmetrical Suzuki-Miyaura-type sp(3)-sp(3) C-C bond formations between allyl carbonates and nontoxic allyl, allenyl, or propargyl boronates. This report represents the first use of these types of boronic esters in this particular context. The present transformations proceeded with high selectivity under remarkably mild conditions, and various functional groups including an aldehyde function proved to be compatible. In addition, several boronates were found to display very unusual reactivity patterns; the higher reactivity of boron as apposed to silicon was clearly demonstrated as well. Finally, the inherent problem of beta-hydride elimination associated with intermediary allyl-Pd species was addressed by employing a commercially available Ni(0) catalyst.


Biological half-life of iodine in adults with intact thyroid function and in athyreotic persons.
A joint project between the Human Monitoring Laboratory (HML) and the Ottawa Hospital has measured the retention of 131I in patients who have received the radioiodine diagnostically. Thirty-nine subjects with intact thyroid glands and nine athyreotic subjects were measured in the HML's whole-body/thyroid counter to determine the retention of 131I following its medical administration. The average biological half-life of 131I in 26 euthyroid subjects was found to be 66.1+/-6.3 days which may he statistically significantly lower than the ICRP recommended value of 80 days. Nine hyperthyroid patients had a mean biological half-life of 38.2+/-8.6 days and in three hypothyroid patients the corresponding value was 29.3+/-8.8 days. Thyroid 131I uptake was measured in a conventional clinical fashion at the Ottawa Hospital Civic campus 24 h after oral administration of the radioiodine using a collimated thick sodium iodide detector placed over the neck anteriorly. Measured values were 10.144+/-0.009, 0.314+/-0.035 and 0.045+/-0.010 of the administered dose in euthyroid, hyperthyroid and hypothyroid patients respectively. The euthyroid range at the hospital is 0.06 - 0.22. Uptake was significantly lower for the euthyroid group than the ICRP value of 0.3. The radioiodine retention in athyreotic subjects followed a two compartment model with biological half-lives of 1.0+/-1.2 days and 18.4+/-1.1 days.


Patient preferences and urologist recommendations among local-stage prostate cancer patients who present for initial consultation and second opinions.
This study describes urologist recommendations for treatment among local-stage prostate cancer patients presenting for initial management consultations versus second opinions. We hypothesized that urologists present a wider range of management recommendations and are less likely to consider the patient preference during the initial consultation. Newly diagnosed local-stage prostate cancer patients and their urologists participated in a survey at urology practices in three states. The urologist's survey included questions about the patient's clinical status, treatments discussed and recommended, and factors that influenced the urologist's recommendations. Of the 238 eligible patients, 95 men presented for an initial consultation, and 143 men presented for a second opinion. In multivariate analysis, urologists recommended 0.52 more treatments (standard error 0.19, P<0.001) during an initial consultation as opposed to a second opinion. The proportion recommending surgery increased from 71-91% (initial consultation versus second opinion setting). Among initial consultations, 59% had low-risk disease, and urologists' recommendations included surgery (80%), external radiation (38%), brachytherapy (seeds) (52%), and active surveillance (25%). Of the 54% with low-risk disease in a second opinion consultation, urologists' recommendations included surgery (90%), external radiation (16%), brachytherapy (14%), and active surveillance (16%). In second opinion settings urologists discussed fewer treatment options and recommended surgery more often. These findings also applied to men with low-risk prostate cancer.


Development of Hepatocellular Carcinoma During Nivolumab Treatment for Recurrent Non-Small Cell Lung Cancer: A Case Report.
Nivolumab, a monoclonal antibody targeting programmed cell death 1 (PD-1), is the standard second-line therapy for advanced non-small cell lung cancer (NSCLC). In the current immunotherapy era, it is often difficult to evaluate the therapeutic effect, disease progression, and pseudo-enlargement of the tumor or the emergence of another etiology. In the present report, we describe a 79-year-old patient with hepatocellular carcinoma (HCC) newly detected during nivolumab treatment for recurrent NSCLC. When the patient was 73 years old, he had suffered from NSCLC and received concurrent chemoradiotherapy comprising cisplatin and docetaxel, achieving a complete response. Six years after the chemoradiotherapy, the patient had multiple lung and hepatic lesions. We thus started the treatment with nivolumab for recurrent NSCLC. All those lesions responded to nivolumab over nine cycles. By contrast, a lesion was newly detected in the medial segment of left hepatic lobe, liver segment 4 (S4), and was gradually getting larger, as judged by computed tomographic scan. Liver biopsy revealed the growing lesion to be a well-differentiated HCC. Consequently, the patient was treated with radiofrequency ablation to HCC, while nivolumab treatment was continued for NSCLC. Immunohistochemical analysis of the HCC specimens revealed nuclear accumulation of β-catenin compared with normal liver cells and undetectable expression of program death ligand 1 (PD-L1). Such expression profiles of β-catenin and PD-L1 in HCC may be responsible for the resistance against nivolumab treatment. Immunohistochemical features of the biopsy specimens may be predictive of the effectiveness of the immunotherapy in HCC.


Follow-up study of conservative treatment for atlantoaxial rotatory displacement.
Rotatory displacement of the atlantoaxial joint is one of the causes of torticollis in children. Some of these cases show persistent symptoms and may lead to rotatory fixation; however, only a few studies have been directed to the prognosis of atlantoaxial rotatory displacement after conservative treatment. Clinical and radiographic reviews were performed in 35 patients (16 male and 19 female) with rotatory displacement of the atlantoaxial joint. The mean age at admission was 6.5 (range: 2-12) years old, and the mean follow-up period was 3.4 (1.4-5.8) years. All patients successfully achieved reduction after 2 to 3 weeks of continuous halter traction; however, 9 patients (25.7%) experienced recurrence, and 7 patients (20.0%) had a slight torticollis at follow-up. The duration of symptoms before treatment affected the recurrence rate, and the torticollis was apt to remain in cases with severe displacement at admission.


PC12 cells overexpressing the insulin receptor undergo insulin-dependent neuronal differentiation.
Stimulation of phaeochromocytoma PC12 cells by nerve growth factor leads to growth arrest and neuronal differentiation, whereas insulin induces various metabolic responses such as metabolism of glucose and lipids. Moreover, both insulin and epidermal growth factor stimulate the proliferation of PC12 cells. In spite of their different biological effects, nerve growth factor, insulin and epidermal growth factor induce very similar early responses in PC12 cells. Stimulation with nerve growth factor leads to the sustained activation and nuclear translocation of mitogen-activated protein (MAP) kinase. By contrast, both insulin and epidermal growth factor induce the transient activation of MAP kinase, without pronounced nuclear translocation of the enzyme. We have investigated whether the differential activation of signaling pathway components can account for the distinct cellular responses to these different growth factors. By overexpressing insulin receptors in PC12 cells, we observed insulin-dependent neurite outgrowth, similar to that induced by nerve growth factor in both non-transfected and overexpressing cells. Overexpression of insulin receptors in PC12 cells leads to a more pronounced, but similar pattern of insulin-induced tyrosine-phosphorylated proteins in PC12 cells, including enhanced recruitment of Grb2/Sos into a complex with either Shc or IRS1. MAP kinase activation in response to insulin stimulation of cells overexpressing the insulin receptor is similar to MAP kinase activation in response to NGF stimulation of parental or overexpressing PC12 cells: the activation is prolonged and nuclear translocation of the enzyme occurs. The differential subcellular localization and duration of MAP kinase activation induced by insulin and NGF may explain the difference in the biological actions of these two factors on PC12 cells. Our results show that the strength of the signal generated by a receptor with tyrosine kinase activity can influence the downstream signaling pathway, leading to cell differentiation instead of cell proliferation.


Simulation of the Parameters Effecting the Water Quality Evolution of Xuanwu Lake, China.
After years of water environment improvement, China's water quality has improved to some extent in recent years. However, different water areas have different characteristics of water pollution. The paper used mathematical models to investigate the influence of different parameters on the water quality of Xuanwu Lake, China. The predominant focus was on the nutrients concentration due to changing the amount of pollutants, degradation coefficient, water diversion discharge and diffusion coefficient. The results showed that the amount of pollutants had the most significant impact, followed by the degradation coefficient. The total phosphorus and total nitrogen concentrations of Xuanwu Lake increased with the increase of the amount of pollutants. The water quality of Xuanwu Lake decreased significantly with the increase of degradation coefficient. Increasing the water diversion discharge will not only make a big difference in water quality, but it will also worsen the water quality. The effect of the amount of pollutants on Xuanwu Lake total phosphorus and total nitrogen is 4.1 and 5.7 times that of water diversion discharge. The influence of total phosphorus and total nitrogen in the degradation coefficient scheme is 3.5 and 6.2 times that of the water diversion discharge scheme. The diffusion coefficient has almost no effect on the water quality of Xuanwu Lake. From the practical difficulty and implementation effect of water environment improvement, the order of water quality improvement effect from good to bad is as follows: the amount of pollutants scheme, degradation coefficient scheme, water diversion scheme, diffusion coefficient scheme. Under the circumstance of limited water diversion, the lake will effectively improve the water quality. Reducing the discharge of pollutants is the fundamental measure to control water environment problems, and water diversion is an auxiliary measure to improve the water ecology. It will become a trend to combine the reduction of pollutant discharge and water transfer for water environment improvement. This paper is of significance for improving the water quality of Xuanwu Lake, and it also provides a scientific method for water environment improvement of water diversion projects.


Verteporfin-based photodynamic therapy overcomes gemcitabine insensitivity in a panel of pancreatic cancer cell lines.
Pancreatic cancer is notoriously difficult to treat and resistant to virtually all therapeutics including gemcitabine, the standard front line agent for palliative chemotherapy. Early clinical studies point to a potential role for photodynamic therapy (PDT) in the management of this deadly disease. Here we examine PDT with verteporfin for treatment of cells that are nonresponsive to gemcitabine and identify intracellular and extracellular factors that govern sensitivity to each modality. Using MTS we assess cytotoxicity of verteporfin-PDT in gemcitabine-treated nonresponsive populations from a panel of five pancreatic cancer cell lines representing a range of tumor histopathology and origin. We conduct Western blots for pro-/anti-apoptotic proteins bax and Bcl-XL to identify factors relevant to PDT and gemcitabine sensitivity. To examine the role of extracellular matrix influences we compare response to each modality in traditional cell culture conditions and cells grown on a laminin-rich basement membrane. All cell lines have gemcitabine nonresponsive populations (17-33%) at doses up to 1 mM while moderate total verteporfin PDT doses (1-6 µM J/cm2) produce nearly complete killing. Our data shows that cells that are nonresponsive to sustained gemcitabine incubation are sensitive to verteporfin PDT indicating that the latter is agnostic to gemcitabine sensitivity. Verteporfin-based PDT decreases Bcl-XL and increases the bax/Bcl-XL ratio toward a pro-apoptotic balance. Insensitivity to gemcitabine is increased in cells that are adherent to basement membrane relative to traditional tissue culture conditions. Collectively these results indicate the ability of verteporfin-based PDT to bypass intracellular and extracellular cues leading to gemcitabine resistance and point to the emerging role of this therapy for treatment of pancreatic cancer.


Redox properties of the ferricyanide ion on electrodes coated with layer-by-layer thin films composed of polysaccharide and poly(allylamine).
Polyelectrolyte multilayer thin films were prepared by an alternate deposition of poly(allylamine hydrochloride) (PAH) and anionic polysaccharides {carboxymethylcellulose (CMC) and alginic acid (AGA)} on the surface of a gold (Au) disk electrode, and the binding of ferricyanide [Fe(CN)(6)](3)(-) and hexaammine ruthenium ions [Ru(NH(3))(6)](3+) to the films was evaluated. Poly(acrylic acid) (PAA) was also employed as a reference polyanion bearing carboxylate side chains. A quartz-crystal microbalance study showed that PAH-CMC and PAH-AGA multilayer films grow exponentially as the number of depositions increases. The thicknesses of five bilayers of (PAH-CMC)(5) and (PAH-AGA)(5) films were estimated to be 150 +/- 20 and 90 +/- 15 nm, respectively, in the dry state. The PAH/polysaccharide multilayer film-coated Au electrodes exhibited a redox response to the [Fe(CN)(6)](3)(-) ion dissolved in solution, irrespective of the sign of the surface charge of the film, suggesting the high permeability of the films to the [Fe(CN)(6)](3)(-) ion. In contrast, the PAH-PAA film-coated Au electrodes exhibited a redox response only when the outermost surface of the film was covered with a positively charged PAH layer. However, the permeation of the [Ru(NH(3))(6)](3+) cation was severely suppressed for all of the multilayer films. It was possible to confine the [Fe(CN)(6)](3)(-) ion in the films by immersing the film-coated electrodes in a 1 mM [Fe(CN)(6)](3)(-) solution for 15 min. Thus, the [Fe(CN)(6)](3)(-)-confined electrodes exhibited a cyclic voltammetric response in the [Fe(CN)(6)](3)(-) ion-free buffer solution. The loading of the [Fe(CN)(6)](3)(-) ion in the films was higher when the surface charge of the film was positive and increased with increasing film thickness. It was also found that the [Fe(CN)(6)](3)(-) ion confined in the films serves as an electrocatalyst that oxidizes ascorbic acid in solution.


Health Literacy in Portugal: Results of the Health Literacy Population Survey Project 2019-2021.
Health literacy entails the knowledge, motivation, and competencies to access, understand, appraise, and apply health information in order to make judgments and decisions in everyday life concerning health care, disease prevention, and health promotion to maintain or improve quality of life throughout the life course. It has become an essential concept in public health. It is considered a modifiable determinant of health decisions, health behaviors, health, and healthcare outcomes. Prior studies suggest highly variable levels of health literacy across European countries. Assessing and monitoring health literacy is critical to support interventions and policies to improve health literacy. This study aimed to describe the process of adaptation to Portugal of the short-form version of the Health Literacy Survey (HLS19-Q12) from the Health Literacy Population Survey Project 2019-2021, also establishing the health literacy levels in the Portuguese population. The sample comprised 1247 valid cases. The survey consisted of a brief questionnaire on the determinants of health literacy, plus the HLS19-Q12 questionnaire and the specific health literacies packages on digital health literacy, navigational health literacy, and vaccination health literacy. The results suggest that 7 out of 10 people in Portugal (mainland) have high health literacy levels and support the results of other studies concerning the main socioeconomic determinants of general health literacy. Furthermore, the results suggest that "navigation in the health system" tasks are the most challenging tasks regarding specific health literacies. The overall data suggest the HLS19-Q12 as a feasible measure to assess health literacy in the Portuguese population. Thus, it can be used in Portugal to assess the population's needs and monitor and evaluate policies and initiatives to promote health literacy by addressing its societal, environmental, personal, and situational modifiable determinant factors.


[Critical care management and thinking of perihematomal edema after intracerebral hemorrhage].
The prognosis of patients with spontaneous intracerebral hemorrhage (sICH) is poor. It is of great significance to improve the neurological function of these patients and make them return to society. However, to date, no treatment has been proved to significantly improve the neurological prognosis of sICH patients. The perihematomal edema (PHE) is a quantifiable marker of secondary brain injury (SBI) after ICH. It is associated with dysfunction of ion channels of vascular endothelial cells, inflammatory response induced-blood brain barrier dysfunction, and iron deposition caused by red blood cell degradation after ICH. Given that the space-occupying effect of PHE, the direct relation with SBI, long growth course and variable growth of PHE among individuals, interrupting the expansion of PHE has become a therapeutic target to improve neurological outcomes in ICH patients. Conducting an integrated and individualized strategy of critical care management and performing the corresponding pre-clinical and translational clinical research targeting the pathophysiological mechanism, nature course, and risk factors of PHE deserves further exploration.


Influence of needle gauge on in vivo ultrasound and microbubble-mediated gene transfection.
Ultrasound and microbubble-mediated gene transfection are potential tools for safe, site-selective gene therapy. However, preclinical trials have demonstrated a low transfection efficiency that has hindered the progression of the technique to clinical application. In this paper it is shown that simple changes to the method of intravenous injection can lead to an increase in transfection efficiency when using 6-MHz diagnostic ultrasound and the ultrasound contrast agent, SonoVue. By using needles of progressively smaller gauge, i.e., larger internal diameter (ID), from 29 G (ID 0.184 mm) to 25 G (ID 0.31 mm), the transfection of a luciferase plasmid (pGL4.13) was significantly increased threefold in heart-targeted female CD1 mice. In vitro work indicated that the concentration and size distribution of SonoVue were affected by increasing needle gauge. These results suggest that the process of systemic delivery alters the bubble population and adversely affects transfection. This is exacerbated by using high-gauge needles. These findings demonstrate that the needle with the largest possible ID should be used for systemic delivery of microbubbles and genetic material.