A mathematical formula to calculate the theoretical range of motion for total hip replacement.
The reduced range of motion (ROM) resulting from total hip replacement (THR) leads to frequent prosthetic impingement, which may restrict activities of daily living and cause subluxation and dislocation. Therefore, to know the ROM of THR is very important in clinical situations and in the design of prostheses. THR involves a pure ball and socket joint. We created a mathematical formula to calculate the theoretical ROM of THR limited by the prosthetic impingement. The ROM of THR is governed by the following five factors, (1) The prosthetic ROM (oscillation angle: obtained from company data), (2) cup abduction (3) cup anterior opening, (4) the angle of the femoral neck component from the horizontal plane, and (5) the femoral neck anteversion. The last 4 factors are able to be obtained from anterior-posterior, axial X-rays and CT of the patient's THR. The objective was to create mathematical formulas that could accurately and quickly calculate the ROM of THR. By entering the five values into a computer programmed with the formulas, one could obtain the ROM for the THR. This reveals the effect on ROM of the oscillation angle and the interaction of ROM with cup abduction, anterior opening and neck anteversion. Furthermore this readily would enable a clinical evaluation of the possibility of postoperative dislocation and help in postoperative rehabilitation. The calculated numerical values of ROM by these mathematical formulas were successfully compared with the ROMs obtained from 3-dimensional computer graphics (3D-CG).


Mortality associated with implantation and management of intrathecal opioid drug infusion systems to treat noncancer pain.
In 2006, the authors observed a cluster of three deaths, which circumstances suggested were opioid-related, within 1 day after placement of intrathecal opioid pumps for noncancer pain. Further investigation suggested that mortality among such patients was higher than previously appreciated. The authors performed investigations to quantify that mortality and compare the results to control populations, including spinal cord stimulation and low back surgery. After analyzing nine index cases--three sentinel cases and six identified by a prospective strategy--the authors used epidemiological methods to investigate whether mortality rates reflected patient- or therapy-related differences. Mortality rates after intrathecal opioid therapy and spinal cord stimulation were derived by correlating Medtronic device registration data with de-identified data from the Social Security Death Master File. Aggregate demographic and comorbidity data were obtained from Medicare and United Healthcare population databases to examine the influence of demographics and comorbidities on mortality. Device registration and Social Security analyses revealed an intrathecal opioid therapy mortality rate of 0.088% at 3 days after implantation, 0.39% at 1 month, and 3.89% at 1 yr-a higher mortality than after spinal cord stimulation implants or after lumbar diskectomy in community hospitals. Demographic, illness profile, and mortality analyses of large databases suggest, despite limitations, that excess mortality was related to intrathecal opioid therapy, and could not be fully explained by other factors. These findings were consistent with the nine index cases that revealed that respiratory arrest caused or contributed to death in all patients. No device malfunctions associated with overinfusion were identified among cases where data were available. Patients with noncancer pain treated with intrathecal opioid therapy experience increased mortality compared to similar patients treated by using other therapies. Respiratory depression as a consequence of intrathecal drug overdosage or mixed intrathecal and systemic drug interactions is one plausible, but hypothetical mechanism. The exact causes for patient deaths and the proportion of those deaths attributable to intrathecal opioid therapy remain to be determined. These findings, although based on incomplete information, suggest that it may be possible to reduce mortality in noncancer intrathecal opioid therapy patients.


Pandemic influenza A (H1N1) in HIV-1-infected patients.
To characterize the clinical presentation, course and mortality of pandemic influenza in HIV-1-infected patients in Santiago, Chile. Prospective observational study. Thirty patients were included (three hospitalized), 93% were on HAART, mean CD4(+) cell count was 423 cells/μl and viral load was undetectable in 77% of patients. All patients had fever, 90% had cough, 80% had myalgias, 70% had pharyngeal congestion, 47% had coryza, 47% had odynophagia, 37% had headache and 23% had vomiting. Four patients developed pneumonia. All patients received antiviral therapy and no patient died. HIV patients infected by the new influenza A pandemic (H1N1) virus behave similarly to the general population.


[Meta analysis on etiological relationship between human papillomavirus and esophageal carcinoma].
To study the relationship between human papillomavirus (HPV) and esophageal cancer development in China. We searched and collected the published articles in Chinese related to HPV and esophageal cancer, and selected the articles with the PCR approach to detect HPV in the esophageal cancer specimens. We filtered our publication collection with standards as (1) PCR as the detection approach, (2) specimens as the paraffin-embedded sections, and (3) description of the primer in the experiments, and fifteen articles were enrolled for our meta-analysis. Among the articles, totally 980 specimens were tested, and 460 were HPV positive with the average HPV prevalence was 46.9% (95% CI: 43.8%-50.0%), varied from 8.3%-69.8% in the different locations. On the other hands, among 556 specimens whose HPV detection spectrum included HPV16, 139 showed the positivity of HPV16, the average prevalence was 25.0%, (95% CI: 21.4%-28.6%) varied from 4.4%-63.4% dependent on the locations; among 485 specimens whose HPV detection spectrum included HPV18, thirty-three specimens showed the positivity of HPV18, the average prevalence was 6.8% (95% CI: 4.6%-9.0%) varied from 0%-19.0% dependent on the locations. Third, among the fifteen articles enrolled in the meta-analysis, four articles used the same primer set for HPV detection in totally 406 paraffin-embedded specimens with the prevalence of 40.2% (95% CI: 36.0%-45.4%) varied from 20.3%-67.6% in different locations. Our analysis result suggested the HPV prevalence in the esophageal cancer samples of China and clued the possible etiological relationships between HPV infection and the esophageal cancer development.


Coexistence of pathogens in host-seeking and feeding ticks within a single natural habitat in Central Germany.
The importance of established and emerging tick-borne pathogens in Central and Northern Europe is steadily increasing. In 2007, we collected Ixodes ricinus ticks feeding on birds (n = 211) and rodents (n = 273), as well as host-seeking stages (n = 196), in a habitat in central Germany. In order to find out more about their natural transmission cycles, the ticks were tested for the presence of Lyme disease borreliae, Anaplasma phagocytophilum, spotted fever group (SFG) rickettsiae, Francisella tularensis, and babesiae. Altogether, 20.1% of the 680 ticks examined carried at least one pathogen. Bird-feeding ticks were more frequently infected with Borrelia spp. (15.2%) and A. phagocytophilum (3.2%) than rodent-feeding ticks (2.6%; 1.1%) or questing ticks (5.1%; 0%). Babesia spp. showed higher prevalence rates in ticks parasitizing birds (13.2%) and host-seeking ticks (10.7%), whereas ticks from small mammals were less frequently infected (6.6%). SFG rickettsiae and F. tularensis were also found in ticks collected off birds (2.1%; 1.2%), rodents (1.8%; 1.5%), and vegetation (4.1%; 1.6%). Various combinations of coinfections occurred in 10.9% of all positive ticks, indicating interaction of transmission cycles. Our results suggest that birds not only are important reservoirs for several pathogens but also act as vehicles for infected ticks and might therefore play a key role in the dispersal of tick-borne diseases.


Renal tubular basement membrane changes in tubulointerstitial damage in patients with glomerular diseases.
Injury to renal tubules and interstitium occur in various glomerular diseases, leading to functional impairment. Tubular basement membrane (TBM) is an important component in maintaining tubular epithelial cell integrity. Because ultrastructural changes in these structures had not been studied in detail, the authors analyzed 30 patients with various types of glomerular diseases, including minimal change disease (MCD), focal segmental glomerular sclerosis, IgA nephropathy, diffuse proliferative glomerulonephritis, membranous nephropathy, and lupus nephritis, by light, electron, and immunofluorescence microscopy. Ultrastructural changes in the TBM were studied and morphometric measurements were performed. The tubular basement membranes showed membranous structures, lucent or lytic areas, and tubular epithelial detachment. There was significant linear correlation between these tubular basement membrane changes and terminal complement complex neoantigens. The interstitial widening was due to banded collagen fibers, with anchoring fibers in the TBM. The various glomerular diseases lead to tubulointerstitial damage via changes in the TBM, leading to renal dysfunction.


The moral self and moral duties.
Recent research has begun treating the perennial philosophical question, "what makes a person the same over time?" as an empirical question. A long tradition in philosophy holds that psychological continuity and connectedness of memories are at the heart of personal identity. More recent experimental work, however, has suggested that persistence of moral character, more than memories, is perceived as essential for personal identity. While there is a growing body of evidence supporting these findings, a recent critique suggests that this research program conflates personal identity with mere similarity. To address this criticism, we explore how loss of someone's morality or memories influences perceptions of identity change and perceptions of moral duties toward the target of the change. We present participants with a classic "body switch" thought experiment and after assessing perceptions of identity persistence, we present a moral dilemma, asking participants to imagine that one of the patients must die (Study 1) or be left alone in a care home for the rest of their life (Study 2). Our results highlight the importance of the continuity of moral character, suggesting that lay intuitions are tracking (something like) personal identity, not just mere similarity.


Nitric oxide-mediated proteasome-dependent oligonucleosomal DNA fragmentation in Leishmania amazonensis amastigotes.
Resistance to leishmanial infections depends on intracellular parasite killing by activated host macrophages through the L-arginine-nitric oxide (NO) metabolic pathway. Here we investigate the cell death process induced by NO for the intracellular protozoan Leishmania amazonensis. Exposure of amastigotes to moderate concentrations of NO-donating compounds (acidified sodium nitrite NaNO(2) or nitrosylated albumin) or to endogenous NO produced by lipopolysaccharide or gamma interferon treatment of infected macrophages resulted in a dramatic time-dependent cell death. The combined use of several standard DNA status analysis techniques (including electrophoresis ladder banding patterns, YOPRO-1 staining in flow cytofluorometry, and in situ recognition of DNA strand breaks by TUNEL [terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling] assay) revealed a rapid and extensive fragmentation of nuclear DNA in both axenic and intracellular NO-treated amastigotes of L. amazonensis. Despite some similarities to apoptosis, the nuclease activation responsible for characteristic DNA degradation was not under the control of caspase activity as indicated by the lack of involvement of cell-permeable inhibitors of caspases and cysteine proteases. In contrast, exposure of NO-treated amastigotes with specific proteasome inhibitors, such as lactacystin or calpain inhibitor I, markedly reduced the induction of the NO-mediated apoptosis-like process. These data strongly suggest that NO-induced oligonucleosomal DNA fragmentation in Leishmania amastigotes is, at least in part, regulated by noncaspase proteases of the proteasome. The determination of biochemical pathways leading up to cell death might ultimately allow the identification of new therapeutic targets.


A patient with respiratory toxigenic diphtheria in Greece after more than 30 years.
The introduction of treatment and systematic vaccination has significantly reduced diphtheria mortality; however, toxigenic strains continue to circulate worldwide. The emergence of an indigenous diphtheria case with fatal outcome in Greece, after 30 years, raised challenges for laboratory confirmation, clinical and public health management. Toxigenic Corynebacterium diphtheriae was isolated from an incompletely vaccinated 8-year-old boy with underlying conditions. The child passed away due to respiratory distress syndrome, before the administration of diphtheria antitoxin (DAT). All close contacts in family, school and hospital settings were investigated. Pharyngeal swabs were obtained to determine asymptomatic carriage. Chemoprophylaxis was given for 7 days to all close contacts and a booster dose to those incompletely vaccinated. Testing revealed a classmate, belonging to a subpopulation group (Roma), and incompletely vaccinated, as an asymptomatic carrier with an indistinguishable toxigenic strain (same novel multilocus sequence type, designated ST698). This case highlights the role of asymptomatic carriage, as the entry of toxigenic strains into susceptible populations can put individuals and their environment at risk. Maintenance of high-level epidemiological and microbiological surveillance, implementation of systematic vaccination in children and adults with primary and booster doses, availability of a DAT stockpile, and allowing timely administration are the cornerstone to prevent similar incidents in the future.


Hepatectomy As A First Choice Treatment For Liver Metastasis From Gastric Cancer: A Single Center Experience.
Indication of hepatectomy for liver metastases from gastric cancer (LMGC) is still controversial despite many papers favoring surgery. The aim of this study is to claim that we should accept hepatectomy as first choice treatment for LMGC. It is important to have a consensus on this matter for surgeons to treat LMGC properly. Fifty three patients undergoing hepatectomy for LMGC from 1990 through 2010 were retrospectively analysed for survival and prognostic factors. Analyses were made on size, multiplicity, synchronicity and positive surgical margin as liver metastasis factors. Serosal invasion, node metastasis, histological differentiation and UICC stage were analysed as primary site factors. Multivariate analysis was performed for those positive for univariate analysis. Cumulative 5 year survival rate was 27%. Multiplicity, positive margin and node metastasis (N > 2) yielded significant difference on univariate analysis. On multivariate analysis multiplicity and node metastasis (N > 2) were significant. Hepatectomy for LMGC is potentially curative and should be regarded as first choice. Solitary and N < 3 are good prognostic factors.


Meat fermentation at a crossroads: where the age-old interplay of human, animal, and microbial diversity and contemporary markets meet.
Despite being part of the now often unfavourably perceived category of processed meats, fermented meats remain of substantial nutritional, economic, and cultural importance in today's foodscapes. This translates into a vast assortment of different products. Fermentation is driven by microorganisms (e.g. in fermented sausages), although the terminology is sometimes used to also designate products in which microbial contributions are less dominant and that depend primarily on the activity of endogenous meat enzymes (e.g. in raw hams). A summary is given of the main microbial groups that characterize various types of meat and, in particular, their fermented derivatives. Moreover, it is argued that producers of fermented meat products struggle to adapt to a contemporary dietary context of change. On the one hand, they wish to reassure consumers by reaffirming the position of fermented meat products as traditional strongholds. On the other hand, producers are trying to alleviate some of the perceived concerns through technological innovation, for instance related to the impact of processing on food safety and health. This review raises the point that these sometimes contradictory trends can affect the choice of meat type, ingredients, and processing parameters, and how these choices, in turn, can affect microbial diversity.


Potential reproductive toxicity of Largehead Atractylodes Rhizome, the most commonly used Chinese medicine for threatened miscarriage.
Largehead Atractylodes Rhizome (LAR) is the most commonly used Chinese medicine to prevent early pregnancy loss due to threatened miscarriage. However, its safety profile during pregnancy is still not available. Here we aimed to identify the potential adverse effects of LAR on embryo-fetal development as well as prenatal and post-natal growth. Pregnant mice, rats and rabbits were orally administered with LAR extracts in various doses (from 1×, 2×, 3× and up to 6× clinical doses) at different gestational periods (implantation, gastrulation, organogenesis, maturation and whole gestation). Maternal effects on weight loss, implantation failure and fetal resorption and perinatal effects on developmental delay, growth restriction and congenital malformations were studied. In mice, with early LAR exposure, a significant decrease in fetal growth parameters and a significant increase in post-implantation loss were identified. With late LAR exposure, significant increases in gestational duration as well as prenatal and post-natal mortality were found. At high clinical doses, congenital skeletal malformations were recorded. In rabbits, fetal resorption, hydrops fetalis and short ear anomaly were observed. No significant adverse effects were found in rats. Potential reproductive toxicity of LAR in pregnant animals was identified within the clinical dose. Caution should be taken in clinical applications of LAR during pregnancy.


Impact of Two Neuronal Sigma-1 Receptor Modulators, PRE084 and DMT, on Neurogenesis and Neuroinflammation in an Aβ1-42-Injected, Wild-Type Mouse Model of AD.
Alzheimer's disease (AD) is the most common form of dementia characterized by cognitive dysfunctions. Pharmacological interventions to slow the progression of AD are intensively studied. A potential direction targets neuronal sigma-1 receptors (S1Rs). S1R ligands are recognized as promising therapeutic agents that may alleviate symptom severity of AD, possibly via preventing amyloid-β-(Aβ-) induced neurotoxicity on the endoplasmic reticulum stress-associated pathways. Furthermore, S1Rs may also modulate adult neurogenesis, and the impairment of this process is reported to be associated with AD. We aimed to investigate the effects of two S1R agonists, dimethyltryptamine (DMT) and PRE084, in an Aβ-induced in vivo mouse model characterizing neurogenic and anti-neuroinflammatory symptoms of AD, and the modulatory effects of S1R agonists were analyzed by immunohistochemical methods and western blotting. DMT, binding moderately to S1R but with high affinity to 5-HT receptors, negatively influenced neurogenesis, possibly as a result of activating both receptors differently. In contrast, the highly selective S1R agonist PRE084 stimulated hippocampal cell proliferation and differentiation. Regarding neuroinflammation, DMT and PRE084 significantly reduced Aβ1-42-induced astrogliosis, but neither had remarkable effects on microglial activation. In summary, the highly selective S1R agonist PRE084 may be a promising therapeutic agent for AD. Further studies are required to clarify the multifaceted neurogenic and anti-neuroinflammatory roles of these agonists.


Modified edentulous ridge expansion technique and immediate implant placement: a 3-year follow-up.
Restoration of the edentulous alveolar ridge with implants often requires the ridge width to be augmented to allow its placement. The aim of this study was to evaluate the split-crest technique, with subepithelial connective tissue graft used as biological barrier, in patients with narrow ridges, focusing on the status of soft and hard tissues and on implant success rate, at 36 months after implant loading. Thirteen patients (6 males and 7 females), ages 32-68 years (mean 49.4 years) with an atrophic maxillary jaw underwent modified edentulous ridge expansion technique for implant placement. A total of 33 Laser-Lok tapered internal implant, were placed in the maxilla. The following parameters were evaluated: (1) initial ridge width (time t0); (2) ridge width at the time of abutment connection (time t1); four months after implants placement, healing abutments were connected and the prosthetic rehabilitation was initiated, and all patients were evaluated clinically and radiographically with periapical radiograph at intervals of 3-6 months for the first year and annually thereafter for 3 years. The ridge width was measured with a cone beam computed tomography. The initial ridge width ranged from 3.5 mm to 7 mm (mean: 4.67 mm), while at the end of the expansion procedure the width ranged from 6.3 mm to 11.0 mm (mean: 8.2 mm). The width gain of the edentulous ridge ranged from 1.45-4.9 mm (mean: 3.5 mm). Two implants became exposed 1 month after surgery. One implant was lost before loading (3%). The diameter of failed implant was 5.8 mm and length was 10.5 mm. The remaining 32 implants were stable and free of complications at the end of the study. Thus, the implant survival rate was 97%. Because no implant failed after loading, the cumulative survival rate of loaded implants was 100%. The minimally invasive regenerative technique presented here avoids the use of bone graft, secondary surgery for soft tissue augmentation, and mechanical expansion devices. However, the follow-up period for outcome evaluation and exiguous patient's number in this series was limited.


School-Based Nutrition Interventions in Children Aged 6 to 18 Years: An Umbrella Review of Systematic Reviews.
Schools are identified as a key setting to influence children's and adolescents' healthy eating. This umbrella review synthesised evidence from systematic reviews of school-based nutrition interventions designed to improve dietary intake outcomes in children aged 6 to 18 years. We undertook a systematic search of six electronic databases and grey literature to identify relevant reviews of randomized controlled trials. The review findings were categorised for synthesis by intervention type according to the World Health Organisation Health Promoting Schools (HPS) framework domains: nutrition education; food environment; all three HPS framework domains; or other (not aligned to HPS framework domain). Thirteen systematic reviews were included. Overall, the findings suggest that school-based nutrition interventions, including nutrition education, food environment, those based on all three domains of the HPS framework, and eHealth interventions, can have a positive effect on some dietary outcomes, including fruit, fruit and vegetables combined, and fat intake. These results should be interpreted with caution, however, as the quality of the reviews was poor. Though these results support continued public health investment in school-based nutrition interventions to improve child dietary intake, the limitations of this umbrella review also highlight the need for a comprehensive and high quality systematic review of primary studies.


GI-Cluster: Detecting genomic islands via consensus clustering on multiple features.
The accurate detection of genomic islands (GIs) in microbial genomes is important for both evolutionary study and medical research, because GIs may promote genome evolution and contain genes involved in pathogenesis. Various computational methods have been developed to predict GIs over the years. However, most of them cannot make full use of GI-associated features to achieve desirable performance. Additionally, many methods cannot be directly applied to newly sequenced genomes. We develop a new method called GI-Cluster, which provides an effective way to integrate multiple GI-related features via consensus clustering. GI-Cluster does not require training datasets or existing genome annotations, but it can still achieve comparable or better performance than supervised learning methods in comprehensive evaluations. Moreover, GI-Cluster is widely applicable, either to complete and incomplete genomes or to initial GI predictions from other programs. GI-Cluster also provides plots to visualize the distribution of predicted GIs and related features. GI-Cluster is available at https://github.com/icelu/GI_Cluster.


Nasopharyngeal oxygen insufflation following pre-oxygenation using the four deep breath technique.
This paper evaluates the effectiveness of nasopharyngeal oxygen insufflation following preoxygenation using the four deep breath technique within 30 s, on the onset of haemoglobin desaturation during the subsequent apnoea. Thirty ASA I or II patients were randomly allocated to one of two groups. In the study group (n = 15), pre-oxygenation was followed by insufflation of oxygen at a flow of 5 l.min(-1) via a nasopharyngeal catheter commenced at the onset of apnoea. In the control group, pre-oxygenation was not followed by nasopharyngeal oxygen insufflation (n = 15). In the control group, SpO2 fell to 95% within a mean (SD) apnoea time of 3.65 (1.15) min, whereas in the study group, SpO2 was maintained in all patients at 100% throughout the 6 min of apnoea, at which point apnoea was terminated and positive pressure ventilation commenced. We conclude that nasopharyngeal oxygen insufflation following pre-oxygenation using the four deep breath technique can delay the onset of haemoglobin desaturation for a significant period of time during the subsequent apnoea.


Side-chain conformations in an unfolded protein: chi1 distributions in denatured hen lysozyme determined by heteronuclear 13C, 15N NMR spectroscopy.
Using a 13C and 15N-labelled sample, multi-dimensional heteronuclear NMR techniques have been carried out to characterise hen lysozyme denatured in 8 M urea at pH 2.0. The measurement of 3J(C',Cgamma) and 3J(N,Cgamma) coupling constants has enabled side-chain chi1 torsion angle populations to be probed in the denatured polypeptide chain. Analysis of the coupling constant data has allowed the relative populations of the three staggered rotamers about chi1 to be defined for 51 residues. The amino acids can broadly be divided into five classes that show differing side-chain conformational preferences in the denatured state. These range from a strong preference for the -60 degrees chi1 rotamer for methionine and leucine (74-79 % population) to a favouring of the +60 degrees chi1 rotamer for threonine (67 % population). The differences in behaviour reflect the steric and electrostatic characteristics of the side-chains concerned. A close agreement is seen between the chi1 populations calculated from the experimental coupling constant data and predictions from the statistical model for a random coil that uses the chi1 torsion angle distributions in a data base of native protein structures. Short-range interactions therefore dominate in determining the local conformational properties of side-chains in a denatured protein. Deviations are, however, observed for many of the aromatic residues involved in hydrophobic clusters within the denatured protein. For these residues the effects of additional non-local interactions in the clusters presumably play a major role in determining the chi1 preferences.


[Cloning and identification of the plasmid replication gene repC in Mesorhizobium huakuii].
The repC gene is the principal initiation protein gene for plasmid replication. We identified the repC-like sequences from Mesorhizobium huakuii strain HN3015 and its derivatives of plasmid curing. Primers of RC1 and RC3 were used to amplify the repC-like sequences by a polymerase chain reaction, the PCR products were obtained and cloned into plasmid vector pMD-18T and then sequenced. Location of the repC sequences on different plasmids in the strains tested was carried out by Southern blotting. The nucleotides homology analysis of the repC gene was carried out using the BLAST. Amino acid sequences were deduced using the ExPASy. Multiple sequences alignments were performed using the ClustalW. Analysis of protein secondary structure was carried out using the PredictProtein. The repC-like sequences were obtained from the strains tested. The sizes of the PCR products were about 750 bp. The results of Southern blotting showed that the repC-like sequences were only associated with a plasmid in the stains tested. The repC sequences of the strains tested showed 100% sequence similarity, but were obviously different from that of other rhizobia strains.


[Application of conceptual mapping in the regulation of access to public health services in the Federal District, Brazil].
Health regulation in the pursuit of equity is the goal of management and requires evaluation methods that improve work processes. The scope of this article is to analyze the application of conceptual mapping in the regulation of access to public health services. It is an exploratory and descriptive study, using a mixed approach, carried out at the Health Regulatory Complex of the Federal District. The data were collected between August and October 2019 and analyzed with the assistance of IRaMuTeQ and Concept Systems® software. There is a convergence of the 25 statements generated by the 71 participants, grouped into 4 clusters, on regulation towards the principle of equity. The healthcare priority level was presented as the focus of regulation and management, the driving force behind the integration of processes. Conceptual mapping is a tool that can support regulation planning and evaluation, as it makes it possible to identify priority points to be worked on by management in improving the regulatory processes identified in this study. These include the training of professionals, the transparency of information and the level of priority healthcare, for effective, equitable, rational and timely access for users of the health system.


Molecular Modification of Fluoroquinolone-Biodegrading Enzymes Based on Molecular Docking and Homology Modelling.
To improve the biodegradation efficiency of fluoroquinolone antibiotics during sewage treatment, fluoroquinolone aerobic, anaerobic and facultative degrading enzymes for fluoroquinolone degradation were modified by molecular docking and homology modelling. First, amino acid residues of the binding sites of degrading enzymes for the target fluoroquinolones ciprofloxacin (CIP), norfloxacin (NOR) and ofloxacin (OFL) were analysed by the molecular docking method. The hydrophobic amino acid residues within 5 Å of the target fluoroquinolone molecules were selected as the modification sites. The hydrophobic amino acid residues at the modified sites were replaced by the hydrophilic amino acid residues, and 150 amino acid sequence modification schemes of the degrading enzymes were designed. Subsequently, a reconstruction scheme of the degrading enzyme amino acid sequence reconstruction scheme was submitted to the SWISS-MODEL server and a selected homology modelling method was used to build a new structure of the degrading enzyme. At the same time, the binding affinities between the novel degrading enzymes and the target fluoroquinolones (represented by the docking scoring function) were evaluated by the molecular docking method. It was found that the novel enzymes can simultaneously improve the binding affinities for the three target fluoroquinolones, and the degradation ability of the six modification schemes was increased by more than 50% at the same time. Among the novel enzymes, the affinity effect of the novel anaerobic enzyme (6-1) with CIP, NOR and OFL was significantly increased, with increases of 129.24%, 165.06% and 169.59%, respectively, followed by the facultative enzyme and aerobic enzyme. In addition, the designed degrading enzymes had certain selectivity for the degradation of the target quinolone. Among the novel enzymes, the binding affinities of the novel anaerobic enzyme (6-3) and CIP, the novel aerobic enzyme (3-6) and NOR, and the novel facultative enzyme (13-6) and OFL were increased by 149.71%, 178.57% and 297.12% respectively. Calculations using the Gaussian09 software revealed that the degradation reaction barrier of the novel degrading enzyme (7-1) and CIP NOR and OFL decreased by 37.65 kcal·mol-1, 6.28 kcal·mol-1 and 6.28 kcal·mol-1, respectively, which would result in efficient degradation of the target fluoroquinolone molecules. By analysing the binding affinity of the degrading enzymes before and after the modification with methanol, it was further speculated that the degradation effect of the modified aerobic degrading enzymes on organic matter was lower than that before the modification, and the increase or decrease in the degradation effect was less than 10%. The mechanism analysis found that the interaction between the modified amino acid residues of the degrading enzymes and the fluoroquinolone molecules increased. The average distance between the amino acid residues and the fluoroquinolone molecules represented a comprehensive affinity effect, and its value was positively correlated with the degradation effect of the novel degrading enzymes.


Redox-active radical scavenging nanomaterials.
Reactive oxygen and nitrogen species play a critical role in many degenerative diseases and in aging. Nanomaterials, especially modified fullerenes and cerium oxide nanoparticles, have been shown to effectively protect mammalian cells against damage caused by increased reactive oxygen or nitrogen species, likely through their direct reaction with superoxide radical, since each of these materials has been shown to act as effective superoxide dismutase mimetics in vitro. This critical review discusses the chemistry of these nanomaterials and the context in which their radical scavenging activities have been studied in biological model systems. Current studies are focused on determining the uptake, metabolism, distribution, toxicity and fate of these nanomaterials in cell and animal model systems. Ultimately if shown to be safe, these nanomaterials have the potential to be used to reduce the damaging effects of radicals in biological systems (101 references).


Activation of phospholipase D induced by hydrogen peroxide in suspension-cultured rice cells.
Hydrogen peroxide (H2O2) (10-100 microM) induced rapid and transient accumulation of phosphatidic acid (PA) in suspension-cultured rice cells. When phospholipase activity in the cellular extract fraction prepared from rice cells treated with H2O2 was assayed in the presence of 1-butanol (0.1%), rapid and transient phosphatidylbutanol (PtdBut) formation was observed. Thus, the H2O2-activated phospholipase was concluded to be phospholipase D (PLD). Furthermore, H2O2 directly induced in vitro PLD activation in the cytosolic fraction without H2O2 treatment. In vitro and in vivo activation of PLD were completely suppressed in the presence of lavendustin A (0.05 mM), a potent inhibitor of protein tyrosine kinase. Phytoalexin biosynthesis induced by N-acetylchitooligosaccharide elicitor was enhanced in the presence of H2O2 (10-100 microM), whereas it was suppressed in the presence of tiron, a potent scavenger of O2-, 1-butanol (0.1%) and lavendustin A (0.05 mM). These results indicate that H2O2-inducible PLD activation enhances signal transduction leading to phytoalexin biosynthesis in rice cells.


Internal migration between Java-Bali and Eastern Indonesia.
"There are two objectives of this study. The first is to describe the demographic and socio-economic characteristics of life-time migrants from Java-Bali and Eastern Indonesia. The second is to examine the employment and education characteristics of life-time migrants from Eastern Indonesia and Java-Bali in order to identify the net effect of inter-regional migration on each area. The study uses data on life-time interprovincial migration." Data for the study are from the 1985 Indonesian Intercensal Survey.


Cognitive deficits in nonretarded adults with fetal alcohol syndrome.
Persons with fetal alcohol syndrome (FAS) who are not mentally retarded often have difficulty qualifying for special educational and vocational services. In this pilot study, 16 nonretarded young adults with FAS were divided into two groups--one with average to above-average IQ and one with borderline to low-average IQ. Participants in both groups manifested clear deficits on neuropsychological measures sensitive to complex attention, verbal learning, and executive function. The frequency and severity of cognitive impairment demonstrated in both FAS groups were greater than what would have been predicted on the basis of IQ alone. The implications of these findings for identification and management of cognitive impairment in individuals with FAS are discussed.


Application of Chitosan and Its Derivative Polymers in Clinical Medicine and Agriculture.
Chitosan is a biodegradable natural polymer derived from the exoskeleton of crustaceans. Because of its biocompatibility and non-biotoxicity, chitosan is widely used in the fields of medicine and agriculture. With the latest technology and technological progress, different active functional groups can be connected by modification, surface modification, or other configurations with various physical, chemical, and biological properties. These changes can significantly expand the application range and efficacy of chitosan polymers. This paper reviews the different uses of chitosan, such as catheter bridging to repair nerve broken ends, making wound auxiliaries, as tissue engineering repair materials for bone or cartilage, or as carriers for a variety of drugs to expand the volume or slow-release and even show potential in the fight against COVID-19. In addition, it is also discussed that chitosan in agriculture can improve the growth of crops and can be used as an antioxidant coating because its natural antibacterial properties are used alone or in conjunction with a variety of endophytic bacteria and metal ions. Generally speaking, chitosan is a kind of polymer material with excellent development prospects in medicine and agriculture.


Atom probe tomography studies on the Cu(In,ga)Se2 grain boundaries.
Compared with the existent techniques, atom probe tomography is a unique technique able to chemically characterize the internal interfaces at the nanoscale and in three dimensions. Indeed, APT possesses high sensitivity (in the order of ppm) and high spatial resolution (sub nm). Considerable efforts were done here to prepare an APT tip which contains the desired grain boundary with a known structure. Indeed, site-specific sample preparation using combined focused-ion-beam, electron backscatter diffraction, and transmission electron microscopy is presented in this work. This method allows selected grain boundaries with a known structure and location in Cu(In,Ga)Se2 thin-films to be studied by atom probe tomography. Finally, we discuss the advantages and drawbacks of using the atom probe tomography technique to study the grain boundaries in Cu(In,Ga)Se2 thin-film solar cells.


Dewetting behavior of polystyrene film filled with (C6H5C2H4NH3)2PbI4.
The dewetting behavior of thin (about 30 nm) polystyrene (PS) films filled with different amount of (C(6)H(5)C(2)H(4)NH(3))(2)PbI(4) (PhE-PbI(4)) on the silicon substrate with a native oxide layer was investigated. For different additive concentrations, PhE-PbI(4) showed different spatial distributions in the PS films, which had a strong influence on the film wettability, dewetting dynamics, and mechanism. With 0.5 wt % additive, PhE-PbI(4) formed a noncontinuous diffusion layer, which caused a continuous hole nucleation in the film. With about 1 wt % additive, a continuous gradient distribution layer of PhE-PbI(4) formed in the film, which inhibited the dewetting. When the concentration is higher (2 wt %), large PhE-PbI(4) aggregates, in addition to the PhE-PbI(4) continuous layer, formed in the film. These large aggregates (larger than radius of gyration of PS) migrated to the interface, resulting in the hole nucleation and eventually the complete dewetting of the film.


Evolutionary relationships among the male and female mitochondrial DNA lineages in the Mytilus edulis species complex.
A novel form of mitochondrial DNA (mtDNA) inheritance has previously been documented for the blue mussel (Mytilus edulis). Female mussels inherit their mtDNA solely from their mother while males inherit mtDNA from both their mother and their father. In males, the paternal mtDNA is preferentially amplified so that the male gonad is highly enriched for the paternal mtDNA that is then transmitted from fathers to sons. We demonstrate that this mode of mtDNA inheritance also operates in the closely related species M. galloprovincialis and M. trossulus. The evolutionary relationship between the male and female mtDNA lineages is estimated by phylogenetic analysis of 455 nucleotides from the large subunit ribosomal RNA gene. We have found that the male and female lineages are highly divergent; the divergence of these lineages began prior to the speciation of the three species of blue mussels. Further, the separation between the male and female lineages is estimated to have occurred between 5.3 and 5.7 MYA.


Twenty years of experience with a clinical ladder: a tool for professional growth, evidence-based practice, recruitment, and retention.
A clinical ladder program was introduced in a 257-bed facility 20 years ago. The program, developed by nurses for nurses, has evolved as integral to the facility's recruitment and retention, professional development, and evidence-based practice initiatives. This clinical ladder program has been used to encourage staff nurses to reach outside of their comfort zone to develop new skills. In this way, it has served as a means to identify leadership potential as a tool toward succession planning. The program provided evidence for the institution's Magnet designation (2004) and again for its bid for redesignation in 2008.


Rivaroxaban Plus Aspirin for Extended Thromboprophylaxis in Acutely Ill Medical Patients: Insights from the MARINER Trial.
Background The MARINER trial evaluated whether postdischarge thromboprophylaxis with rivaroxaban could reduce the primary outcome of symptomatic venous thromboembolism (VTE) or VTE-related death in acutely ill medical patients at risk for VTE. Although aspirin use was not randomized, approximately half of the enrolled patients were receiving aspirin at baseline. We hypothesized that thromboprophylaxis with once-daily rivaroxaban (10 mg or, if creatinine clearance was 30-49 mL/min, 7.5 mg) plus aspirin (R/A) would be superior to placebo without aspirin (no thromboprophylaxis [no TP]). Methods We compared the primary and major secondary outcomes in the intention-to-treat population in four subgroups defined at baseline: (1) R/A ( N = 3,159); (2) rivaroxaban alone ( N = 2,848); (3) aspirin alone ( N = 3,046); and (4) no TP ( N = 2,966). Major bleeding (MB) and nonmajor clinically relevant (NMCR) bleeding were assessed in the safety population on treatment plus 2 days. Results Patients on R/A had reduced symptomatic VTE and VTE-related death compared with no TP (0.76 vs 1.28%, p = 0.042), and experienced less symptomatic VTE and all-cause mortality ( p = 0.005) and all-cause mortality alone ( p = 0.01) compared with no TP. Event incidences for rivaroxaban alone (0.91%) or aspirin alone (0.92%) were similar. MB was low in all groups but lowest in the no TP group. NMCR bleeding was increased with R/A compared with no TP ( p = 0.009). Limitations Aspirin use was not randomized. Conclusion Extended postdischarge thromboprophylaxis with R/A was associated with less symptomatic VTE and VTE-related death compared with no TP in previously hospitalized medical patients at risk for VTE. NMCR bleeding was increased with R/A compared with no TP. These post hoc findings need confirmation in a prospective trial.


Assessment of kidney function in the elderly: a population-based study.
Chronic kidney disease (CKD) affects all age groups, and its prevalence has increased during recent years. CKD is divided into six stages, according to the renal function of patients: 1. Normal renal function without kidney damage; 2. Kidney damage with normal renal function; 3. Mild renal insufficiency; 4. Moderate renal insufficiency or lab tests failure; 5. Severe renal insufficiency or clinical failure; 6. End stage of chronic renal failure. This study was intended to assess renal function in elderly patients and identifying the presence of factors associated with those changes. A cross-sectional population-based study was performed. Elderly patients were surveyed between September 2010 and May 2011. Kidney function was assessed by determining of serum creatinine, and estimation of the glomerular filtration rate by the CKD-EPI equation. In all, 822 elderly were surveyed; 61.6% were women; 92.2% were Caucasian; and most (61.0%) were aged between 60 and 69 years. With regard to the glomerular filtration rate, 26.2% had a normal rate; 60.2% showed a slight decrease; 13.0% a moderate decrease; 0.5% severe kidney function decline; and 0.1% extreme fall. Increasing age was associated with kidney damage by decreased glomerular filtration rate (p < 0.001). In addition, obesity, hypertension and smoking were factors independently associated with reduced glomerular filtration rates. This study found that the great majority of the surveyed elderly had some mild kidney damage, and 13.6% showed moderate to severe dysfunction.


Cryopreservation of shoot tips and cotyledons of the north american ginseng (Panax quinquefolius l.).
North American ginseng (NAG) (Panax quinqueolius L.) is a medicinal plant in high demand due to its health benefits. Cryopreservation is a good alternative for long-term conservation of NAG germplasm. Pretreatments of shoot tips (0.8-1 mm) and cotyledons (1-2 mm) on sucrose and abscisic acid (ABA) enriched medium were tested to determine the effects on regrowth following cryopreservation in liquid nitrogen. The maximum regrowth (60 percent) following PVS2 vitrification occurred with shoot tips after three weeks of cold acclimation and pretreatment on sucrose (0.3 M) or a combination of ABA (0.1 M) and sucrose in the third week. Cotyledon recovery was best with the combination pretreatment. Shoot tips showed normal development and cotyledons produced embryogenic callus after the cryopreservation process. This is the first report on cryopreservation of shoot tips and cotyledons of Panax species. This cryopreservation protocol provides a safe long-term storage method for important NAG selections and makes it possible to use cryopreservation for improving the security of NAG germplasm.


Expression of biologically active human factor VIII using a baculovirus vector.
Factor VIII is a complex, plasma glycoprotein involved in the process of blood coagulation. Production of the recombinant molecule has largely been confined to mammalian cell systems which have, in general, proven to be inefficient producers of factor VIII. The use of a baculovirus expression system may provide increased levels of this glycoprotein, although it is not certain that insect cell-derived factor VIII will be biologically active. The N-linked glycosylation patterns in insect cells, until recently thought to be less complex than in mammalian cells, may influence activity and/or secretory ability. To this end we engineered a B domain-deleted factor VIII cDNA sequence for expression in Spodoptera frugiperda cells. The construct retained the native signal sequence to allow secretion of recombinant protein into the culture medium. Initial studies revealed the production of secreted factor VIII, and this protein was shown to possess coagulation activity. The presence of N-linked oligosaccharide residues was demonstrated, the glycosylated molecule being of a similar size to that expressed in mammalian cells.


[Acupoint injection combined with Vitalstim electrical stimulation for post-stroke dysphagia:a randomized controlled trial].
To observe the clinical efficacy of acupoint injection combined with Vitalstim electrical stimulation for post-stroke dysphagia. A total of 98 patients with dysphagia after first stroke were randomized into an acupoint injection group (35 cases, 2 cases dropped off), an electrical stimulation group (31 cases, 3 cases dropped off) and a combination group (32 cases, 3 cases dropped off). Injection of mecobalamin into Tunyan point, Vitalstim electrical stimulation and the combination of injection of mecobalamin into Tunyan point and Vitalstim electrical stimulation were applied respectively in the 3 groups, once a day, 10 times as one course, 2 courses were required. Before and after treatment, the tongue muscle thickness and video fluoroscopic swallowing study (VFSS) score were observed in the 3 groups. After treatment, the tongue muscle thickness was decreased (P<0.05), the VFSS scores were increased (P<0.05) compared with before treatment in the 3 groups, and the variation of tongue muscle thickness and VFSS score in the combination group was greater than the acupoint injection group and the electrical stimulation group (P<0.05). Both acupoint injection of mecobalamin and Vitalstim electrical stimulation have therapeutic effect on dysphagia after stroke, and the two have synergistic effect.


[War Relief of Japanese Red Cross Nurses in the Lost Battle of Burma].
This paper aims to reveal changes in the relief support of the Japanese Red Cross relief units dispatched to Burma during the Second World War, from the beginning of fighting in Burma to the Japanese withdrawal. Japanese Red Cross relief units began their relief support when Japan invaded Burma in February of 1942. Counterattacks by the British, Indian and Chinese armies from December 1942 caused an increase in the number of patients. There were also many cases of malnutrition and malaria due to the extreme shortage of medical supplies as a result of the Battle of Imphal, which began in March of 1944. Bomb raids became even more intense after the battle ended in July 1944, and patients were carried into bomb shelters and caves on a daily basis. Just prior to invasion by enemy troops, they were ordered to evacuate to neighboring Thailand. Nurses from the Wakayama group hid their identity as members of the Red Cross and evacuated, with 15 out of 23 dying or being reported missing in action.


The role of type I interferons in innate and adaptive immunity against viruses in Atlantic salmon.
Type I IFNs (IFN-I) are cytokines, which play a crucial role in innate and adaptive immunity against viruses of vertebrates. In essence, IFN-I are induced and secreted upon host cell recognition of viral nucleic acids and protect other cells against infection by inducing antiviral proteins. Atlantic salmon possesses an extraordinary repertoire of IFN-I genes encompassing at least six different classes (IFNa, IFNb, IFNc, IFNd, IFNe and IFNf) most of which are encoded by several genes. This review describes recent research on the functions of salmon IFNa, IFNb, IFNc and IFNd. As in mammals, expression of different salmon IFN-I in response to virus infection is dependent on their promoters, properties of the virus and the cell's expression of nucleic acid receptors and interferon regulatory factors (IRFs). While IFNa mainly display local antiviral activity, IFNb and IFNc show systemic antiviral activity. In addition, salmon appears to possess several IFN-I receptors, which show selectivity in binding different IFN-I. This complexity in IFN-I and receptors allows for a large variation in functions of the salmon IFN-I. Studies with intramuscular injection of IFN expression plasmids have recently provided surprising results, which may be of relevance for application of IFN-I in prophylaxis against virus infection. Firstly, injection of IFNc plasmid protected salmon presmolts against virus infection for at least 10 weeks. Secondly, IFN plasmids showed potent adjuvant activity when injected together with a DNA vaccine against infectious salmon anemia virus (ISAV).


A meta-analytic review of Internet gaming disorder and the Big Five personality factors.
Two systematic reviews have been conducted to summarize the literature on Internet Gaming Disorder (IGD) and personality. However, the data was not synthesized statistically, imposing a limit to their conclusions. The current study aimed to extend on the two reviews by conducting a series of five meta-analyses, one for each of the Big Five personality factors, to examine their relationships with IGD. A comprehensive search was conducted on the databases PsycArticles, PsycInfo, and Web of Science from inception to 29 July 2021. The data was analyzed using Meta-Essentials and the random effects model was used to obtain the pooled estimate of the effect size. A total of 12 articles were included (n = 145 to 3389). IGD was not significantly correlated with openness to experience (r = -0.05). However, IGD was negatively correlated with conscientiousness (r = -0.29), extraversion (r = -0.15), and agreeableness (r = -0.17), and positively correlated with neuroticism (r = 0.20). Age moderated the relationships between IGD and openness to experience and conscientiousness. The results were broadly consistent with the DSM-5 IGD criteria and the Big Five personality framework. Future research directions might include examining age as moderator variables, and using appropriate instruments based on the DSM-5 IGD criteria.


An approach to mentoring healthcare play specialist students.
Healthcare play specialists (HPSs) provide therapeutic play programmes for children in healthcare settings. Each HPS student must have a mentor in practice, but most HPSs have received no formal training for their role. This article explores mentoring in the HPS service at Guy's and St Thomas' NHS Foundation Trust. A study day for HPSs was arranged to share best practice and discuss the challenges of mentoring students. Stronger links were built between the higher education institute that delivers the training to HPS students and the trust, and the HPSs were provided with a deeper understanding of what was required of them in their mentoring role. HPSs highlighted the importance of a yearly update on mentoring students.


Serum levels of soluble interleukin-2 receptor in chronic hepatitis C treated with interferon-alpha.
Serum levels of soluble interleukin-2 receptor (sIL-2R) seem to serve as a marker for the activation of T lymphocytes. The aim of this study was to evaluate the clinical significance of such levels in patients with chronic hepatitis C (CHC) treated with interferon. We measured serum levels of sIL-2R in 37 patients with CHC before and after treatment with recombinant interferon-alpha. Serum receptor levels were then compared with the response of the hepatitis C virus (HCV)-RNA level in serum after interferon. Receptor levels were significantly higher in the patients with chronic persistent hepatitis and chronic active hepatitis than in normal controls (p < 0.01). There was a weak correlation between serum sIL-2R and alanine aminotransferase (ALAT) levels (r = 0.14, p = 0.010). Patients were then classified into three groups on the basis of the effect of interferon treatment on HCV-RNA levels in serum: sustained response (SR; n = 21), non-sustained response (NSR; n = 14), and nonresponse (NR; n = 2). Before and during interferon treatment the serum sIL-2R level remained increased in the SR group and in the combined groups with NSR or NR. However, after interferon was withdrawn, the serum sIL-2R decreased in the SR group but remained significantly increased in the combined response group (p < 0.01-0.05). This finding seems to reflect the disappearance of HCV-RNA from the serum of the patients with an SR, and monitoring of sIL-2R levels may therefore be of value as an adjunct to the measurement of serum ALAT and HCV-RNA in evaluating the response to the interferon therapy for CHC.


Protochlorophyll(ide) in a Blue-Green Alga.
During growth under far-red (>650 nm) light, Anacystis nidulans accumulates protochlorophyllide to concentrations about one-tenth of the chlorophyll. From whole cell fluorescence spectra, protochlorophyll(ide) was identified also in another blue-green, and in a red, alga grown in far-red light.


EBSDinterp 1.0: A MATLAB® Program to Perform Microstructurally Constrained Interpolation of EBSD Data.
EBSDinterp is a graphic user interface (GUI)-based MATLAB® program to perform microstructurally constrained interpolation of nonindexed electron backscatter diffraction data points. The area available for interpolation is restricted using variations in pattern quality or band contrast (BC). Areas of low BC are not available for interpolation, and therefore cannot be erroneously filled by adjacent grains "growing" into them. Points with the most indexed neighbors are interpolated first and the required number of neighbors is reduced with each successive round until a minimum number of neighbors is reached. Further iterations allow more data points to be filled by reducing the BC threshold. This method ensures that the best quality points (those with high BC and most neighbors) are interpolated first, and that the interpolation is restricted to grain interiors before adjacent grains are grown together to produce a complete microstructure. The algorithm is implemented through a GUI, taking advantage of MATLAB®'s parallel processing toolbox to perform the interpolations rapidly so that a variety of parameters can be tested to ensure that the final microstructures are robust and artifact-free. The software is freely available through the CSIRO Data Access Portal (doi:10.4225/08/5510090C6E620) as both a compiled Windows executable and as source code.


[Serum concentration of pyridinoline cross-linked carboxy-terminal telopeptide of type-I collagen (ICTP) and carboxyterminal propeptide of human type I procollagen (PICP) in the diagnosis of bone metastases].
Recently discovered bone metabolic markers are expected to play an additional role in the diagnosis of bone metastasis. We measured bone metabolic markers, serum pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) and carboxyterminal propeptide of human type I procollagen (PICP) in 224 patients with breast cancer (106 with bone metastases), 61 patients with prostatic cancer (30 with bone metastases), 45 patients with lung cancer (17 with bone metastases) and 13 patients with miscellaneous cancers (7 with bone metastasis) and compared the values in the presence and absence of bone metastasis. ICTP and PICP increased significantly in patients with bone metastases. By the analysis of sensitivity and specificity, the cut-off levels were considered to be 5.0 ng/ml for ICTP and 140 ng/ml for PICP. In lung cancer (bone metastases are mostly of osteolytic), ICTP was excellent marker in detecting bone metastasis. In breast cancer (bone metastases are mostly of mixed type), ICTP was good in detecting bone metastases. In prostatic cancer (bone metastases are mostly of osteoblastic), ICTP and PICP were good markers in detecting high grade of bone metastases. Over all, ICTP was more sensitive in the diagnosis of bone metastases than PICP. However, both markers were not effective in detecting low grade bone metastases. ICTP and PICP should play a supportive role to imaging modalities in the diagnosis of bone metastases.


Billing for outpatient transplant pharmacy services.
The economic impact of out-patient pharmacy services in a transplant program was evaluated. Full-time kidney transplant pharmacy services were implemented at Providence Sacred Heart Medical Center (PSHMC) in the fall of 2008, with two pharmacists combining hours to provide one full-time-equivalent position. At PSHMC, posttransplantation patients are seen three times per week. The number of patient visits with pharmacists for 2010 was compared with the total number of patient visits. The face-to-face time spent with the patient was translated to a level of billing that was associated with a set reimbursement schedule. For each patient encounter in which a pharmacist was involved, the incremental difference between the nursing and pharmacy levels of billing was examined, as were the levels most often billed by pharmacists. The difference in billing levels between pharmacists and nurses for the same patient encounter was also evaluated. Overall, pharmacist visits accounted for 208 (22%) of the 994 out-patient kidney transplant visits in 2010, with pharmacists billing at a higher level of acuity compared with nursing for the same patient encounter 48% of the time. This translated to an approximate increase of $100 per patient visit. For the one-year study period, pharmacists utilizing facility- fee billing increased out-patient reimbursement by approximately $10,000. By utilizing outpatient facility-fee billing for pharmacy services, the transplant program at PSHMC increased reimbursement in the outpatient setting.


Activation of SGK1 in Endometrial Epithelial Cells in Response to PI3K/AKT Inhibition Impairs Embryo Implantation.
Serum & Glucocorticoid Regulated Kinase 1 (SGK1) plays a fundamental role in ion and solute transport processes in epithelia. In the endometrium, down-regulation of SGK1 during the window of receptivity facilitates embryo implantation whereas expression of a constitutively active mutant in the murine uterus blocks implantation. Here, we report that treatment of endometrial epithelial cells with specific inhibitors of the phosphoinositide 3-kinase (PI3K)/AKT activity pathway results in reciprocal activation of SGK1. Flushing of the uterine lumen of mice with a cell permeable, substrate competitive phosphatidylinositol analogue that inhibits AKT activation (AKT inhibitor III) resulted in Sgk1 phosphorylation, down-regulation of the E3 ubiquitin-protein ligase Nedd4-2, and increased expression of epithelial Na+ channels (ENaC). Furthermore, exposure of the uterine lumen to AKT inhibitor III prior to embryo transfer induced a spectrum of early pregnancy defects, ranging from implantation failure to aberrant spacing of implantation sites. Taken together, our data indicate that the balanced activities of two related serine/threonine kinases, AKT and SGK1, critically govern the implantation process.


Cosmetic results in 242 patients treated by conservative surgery for breast cancer.
The surgery of breast cancer has changed lately in favour of breast conserving treatment, the main purpose of which is to provide good cosmetic results together with radical resection of the tumour. In this paper we describe the cosmetic results obtained in 242 patients treated by conservative surgery (226 quadrantectomies, 93%, and 16 lumpectomies, 7%) for low risk breast cancer. Several of these resections were combined with plastic surgical techniques for residual breast reshaping. The technique chosen depended on the site of tumour, width of resection, and breast volume. The cosmetic assessment was made by the patient and the physician. Our data suggest that better cosmetic results may be obtained when plastic surgical procedures are combined with conservative surgery for breast cancer.


Perceptions of middle school educators in Hawai'i about school-based gardening and child health.
Childhood obesity prevention is a national priority. School-based gardening has been proposed as an innovative obesity prevention intervention. Little is known about the perceptions of educators about school-based gardening for child health. As the success of a school-based intervention depends on the support of educators, we investigated perceptions of educators about the benefits of gardening programs to child health. Semi-structured interviews of 9 middle school educators at a school with a garden program in rural Hawai'i were conducted. Data were analyzed using a grounded theory approach. Perceived benefits of school-based gardening included improving children's diet, engaging children in physical activity, creating a link to local tradition, mitigating hunger, and improving social skills. Poverty was cited as a barrier to adoption of healthy eating habits. Opinions about obesity were contradictory; obesity was considered both a health risk, as well as a cultural standard of beauty and strength. Few respondents framed benefits of gardening in terms of health. In order to be effective at obesity prevention, school-based gardening programs in Hawai'i should be framed as improving diet, addressing hunger, and teaching local tradition. Explicit messages about obesity prevention are likely to alienate the population, as these are in conflict with local standards of beauty. Health researchers and advocates need to further inform educators regarding the potential connections between gardening and health.


New Tunneled Buccal Fat Pad Flap for Palatal Reconstruction.
In the palatal defects due to surgical resection, flap selection is very important for a correct reconstruction. Different methods have been suggested over the time, however the pedicled buccal fat pad is a simple, effective, reliable flap for reconstruction after palate tumor resection. The aim of the present study is to introduce a new surgical technique for palate reconstruction with pedicled buccal fat pad flap exposing the advantages. The Authors performed this procedure in 17 patients in order to treat medium-sized oncologic surgical defect of palate region in the period between 2016 and 2019. Complete wound healing after only 4 weeks without complication after 12 months follow-up was observed. This is the first cases series described with this new technique.


Sensitization Effects of Repurposed Blood Pressure-regulating Drugs on Drug-resistant Cancer Cells.
We investigated drugs that could sensitize KBV20C cancer cells resistant to eribulin or vincristine (VIC) treatment and assessed their associated mechanisms of action. Such cancer cells were known to overexpress P-glycoprotein (P-gp). Considering that reserpine (P-gp inhibitor) plays a regulatory role in patients with high blood pressure, we investigated the effect of low doses of 27 blood pressure-regulating drugs on VIC-resistant KBV20C cells. This was done to identify drugs that could be repurposed for sensitizing antimitotic drug-resistant KBV20C cells at relatively low doses. Fluorescence-activated cell sorting (FACS), annexin V analyses, rhodamine uptake tests and western-blot analysis were performed to further investigate the mechanism of action of such drugs. We found that co-treatment with amiodarone, nicardipine, carvedilol, or vardenafil at low doses could highly sensitize KBV20C cells treated with eribulin or VIC. These drugs reduced cellular viability, increased G2 arrest and up-regulated apoptosis when co-administered with eribulin or VIC. Considering that they sensitize with either co-treatment of eribulin or VIC, we assumed that they can be combined with other antimitotic drugs to sensitize the resistant cancer cells. Through detailed quantitative analysis, we found that eribulin with amiodarone had a higher sensitization effect than eribulin with nicardipine or eribulin with carvedilol. We found that reserpine had the highest P-gp-inhibitory activity, indicating that eribulin- or VIC-reserpine sensitization involves the P-gp inhibitory effects of reserpine. However, we found that amiodarone, nicardipine, carvedilol and vardenafil had very low P-gp inhibitory activity. Moreover, we found that cells co-treated with VIC-carvedilol down-regulated expression of pERK. Highly antimitotic drug-resistant KBV20C cells can be sensitized by co-treatment with the repurposed blood pressure-regulating drugs amiodarone, nicardipine, carvedilol or vardenafil. These findings indicate that the repurposed blood pressure-regulating drugs may potentially be used in drug-resistant cancer patients without any toxic effects due to P-gp inhibition.


C(4) Photosynthesis: Light-dependent CO(2) Fixation by Mesophyll Cells, Protoplasts, and Protoplast Extracts of Digitaria sanguinalis.
Mesophyll cells, protoplasts, and protoplast extracts of Digitaria sanguinalis were used for comparative studies of light-dependent CO(2) fixation. CO(2) fixation was low without the addition of organic substrates. Pyruvate, oxaloacetate, and 3-phosphoglycerate induced relatively low rates (10 to 90 mumoles/mg chlorophyll.hr) of CO(2) fixation when added separately. However, a highly synergistic relationship was found between pyruvate + oxaloacetate and pyruvate + 3-phosphoglycerate for inducing light-dependent CO(2) fixation in the mesophyll preparations. Highest rates of CO(2) fixation were obtained with protoplast extracts. Pyruvate, in combination with oxaloacetate or 3-phosphoglycerate induced light-dependent rates from 150 to 380 mumoles of CO(2) fixed/mg chlorophyll.hr which are equivalent to or exceed reported rates of whole leaf photosynthesis in C(4) species. Concentrations of various substrates required to give half-maximum velocities of CO(2) fixation were determined, with the protoplast extracts generally saturating at the lowest substrate concentrations. Chloroplasts separated from protoplast extracts showed little capacity for CO(2) fixation. The results suggest that CO(2) fixation in C(4) mesophyll cells is dependent on chloroplasts and extrachloroplastic phosphoenolpyruvate carboxylase.The stimulation of pyruvate-induced CO(2) fixation by oxaloacetate and 3-phosphoglycerate is thought to be due to induction of noncyclic electron transport which generates ATP for the conversion of pyruvate to phosphoenolpyruvate by pyruvate Pi dikinase. The primary products of the substrate-induced CO(2) fixation were oxaloacetate and malate, which provides further evidence for carbon fixation through the beta-carboxylation pathway. High rates of light-dependent CO(2) fixation with a significant percentage of (14)C fixed into malate suggest an efficient operation of both photosystems I and II.The substrate inductions are discussed with respect to the proposed role of the mesophyll cell in C(4) photosynthesis, and schemes suggesting the stoichiometry of energy requirements for photosynthetic carbon metabolism in C(4) mesophyll cells are presented.


Efficient Results in Semantic Interoperability for Health Care. Findings from the Section on Knowledge Representation and Management.
To summarize excellent current research in the field of Knowledge Representation and Management (KRM) within the health and medical care domain. We provide a synopsis of the 2016 IMIA selected articles as well as a related synthetic overview of the current and future field activities. A first step of the selection was performed through MEDLINE querying with a list of MeSH descriptors completed by a list of terms adapted to the KRM section. The second step of the selection was completed by the two section editors who separately evaluated the set of 1,432 articles. The third step of the selection consisted of a collective work that merged the evaluation results to retain 15 articles for peer-review. The selection and evaluation process of this Yearbook's section on Knowledge Representation and Management has yielded four excellent and interesting articles regarding semantic interoperability for health care by gathering heterogeneous sources (knowledge and data) and auditing ontologies. In the first article, the authors present a solution based on standards and Semantic Web technologies to access distributed and heterogeneous datasets in the domain of breast cancer clinical trials. The second article describes a knowledge-based recommendation system that relies on ontologies and Semantic Web rules in the context of chronic diseases dietary. The third article is related to concept-recognition and text-mining to derive common human diseases model and a phenotypic network of common diseases. In the fourth article, the authors highlight the need for auditing the SNOMED CT. They propose to use a crowdbased method for ontology engineering. The current research activities further illustrate the continuous convergence of Knowledge Representation and Medical Informatics, with a focus this year on dedicated tools and methods to advance clinical care by proposing solutions to cope with the problem of semantic interoperability. Indeed, there is a need for powerful tools able to manage and interpret complex, large-scale and distributed datasets and knowledge bases, but also a need for user-friendly tools developed for the clinicians in their daily practice.


Typification and taxonomic remarks on five species names in Cytisus (Fabaceae).
This paper deals with the typification and taxonomy of five Mediterranean Cytisus species. Cytisus affinis, C. candidus, and C. spinescens nom. illeg., non Sieber ex Spreng. were described from Sicily by Karel Bořivoj Presl, Cytisus spinescens was described from Apulia (southern Italy) by Curt Polycarp Joachim Sprengel, and C. villosus was described from southern France by Pierre André Pourret (1788). Lectotypes are here designated for Presl and Sprengel's names. A neotype is designated for C. villosus. The taxonomic revision of these five names confirmed that C. villosus Pourr. (= Cytisus affinis C.Presl) is the name to be used for the species occurring in the large part of the Mediterranean countries. Cytisus spinescens Sieber ex Spreng. (≡ C. candidus C.Presl = C. spinescens C.Presl, nom. illeg.) is the correct name for the amphi-adriatic species occurring in peninsular Italy, and along the NE coast of the Adriatic Sea. This species does not occur in Sicily and reference to this latter region in the protologues of both C. spinescens C.Presl and C. candidus C.Presl is a misinterpretation due, possibly, to exchange of labels.


[Computed tomographic angiography in the evaluation of acute pulmonary thromboembolism].
Computed tomographic andiography has becoming the main diagnostic imaging method for the evaluation of patients with suspected pulmonary embolism (PE), due to its high sensitivity and specificity and potential cost-effectiveness. The advances in multidetector computed tomography (MDCT) scanners and optimization of scanning protocols via thinner collimation and faster scanning times have greatly improved the ability to detect PE. The diagnosis is made by direct visualization of a low attenuation filling defect (intraluminal thrombus) that partially or completely occludes a contrast filled artery. Differentiate between acute and chronic PE is often possible through the identification of characteristic findings, such as the diameter of the affected artery and the location and relationship of the thrombus to the vessel walls. Awareness of the major error factors in the CT diagnosis of PE can help further increase the sensitivity and specificity of this imaging method.


Preservation of chitinolytic Pantoae agglomerans in a viable form by cellular dried alginate-based carriers.
Improved viability of Gram-negative bacteria during freeze-dehydration, storage, and soil inoculation is of crucial importance to their efficient application. The chitinolytic Pantoae (Enterobacter) agglomerans strain IC1270, a potential biocontrol agent of soil-borne plant-pathogenic fungi, was used as a model organism to study the efficacy of freeze-dried alginate-based beads (macrocapsules) as possible carriers for immobilized Gram-negative bacterial cells. These macrocapsules were produced by freeze-dehydration of alginate gel spherical beads, in which different amounts of bacteria, glycerol, and colloidal chitin were entrapped. Subsequent drying produced different unexpected structures, pore-size distributions, and changes in the outer and inner appearance of the resultant dried cellular solid. With increasing glycerol content, the proportion of larger pores increased. These structures can be related to changes in the slow-release properties of the dried beads. The amount of glycerol in the beads differed from that in the alginate solution as a result of leakage during the beads' preparation and dehydration. Entrapping 10(9) cells per bead produced from alginate solution containing 30% glycerol and 1% chitin resulted in improved (in comparison to other studies) survival prospects (95%) during freeze-drying. Moreover, immobilization of the bacterium sharply improved its survival in nonsterile irrigated and dry soils compared to bacteria in a water suspension. The results suggest that optimized conservation of Gram-negative bacteria in dry glycerol-containing alginate-based cellular solids is not only possible but applicable for a variety of uses.


Paralogous chemoreceptors mediate chemotaxis towards protein amino acids and the non-protein amino acid gamma-aminobutyrate (GABA).
The paralogous receptors PctA, PctB and PctC of Pseudomonas aeruginosa were reported to mediate chemotaxis to amino acids, intermediates of amino acid metabolism and chlorinated hydrocarbons. We show that the recombinant ligand binding regions (LBRs) of PctA, PctB and PctC bind 17, 5 and 2 l-amino acids respectively. In addition, PctC-LBR recognized GABA but not any other structurally related compound. l-Gln, one of the three amino acids that is not recognized by PctA-LBR, was the most tightly binding ligand to PctB suggesting that PctB has evolved to mediate chemotaxis primarily towards l-Gln. Bacteria were efficiently attracted to l-Gln and GABA, but mutation of pctB and pctC, respectively, abolished chemoattraction. The physiological relevance of taxis towards GABA is proposed to reside in an interaction with plants. LBRs were predicted to adopt double PDC (PhoQ/DcuS/CitA) like structures and site-directed mutagenesis studies showed that ligands bind to the membrane-distal module. Analytical ultracentrifugation studies have shown that PctA-LBR and PctB-LBR are monomeric in the absence and presence of ligands, which is in contrast to the enterobacterial receptors that require sensor domain dimers for ligand recognition.


Challenging parents' myths regarding their children's teething.
The aims of this study were to (i) investigate the parental beliefs about teething signs and symptoms, (ii) investigate the parents' practices used to alleviate teething troubles and (iii) provide an educational basis for dental healthcare providers to better educate parents on this subject. A cross-sectional survey was conducted in a random sample of 1500 parents attending Maternity and Child Health Care Centers. The self-administered questionnaire contained three sections: Section I surveyed parents' and their children's demographic characteristics, Section II aimed to assess the general knowledge and beliefs of parents regarding their children's teething. Section III aimed at investigating the practices that the parents would do to manage teething problems and relieve pain. The analysis of data was carried out using spss computer software. Descriptive statistics and Chi-squared test were utilized. Almost 75% of the participants incorrectly attributed fever, diarrhoea and sleep disturbances to teething, and more than 50% believed systemic symptoms are not related to the process. More than 50% of the participants allowed their children to bite on chilled objects, (76.1%) used systemic analgesics and (65.6%) rubbed the gums with topical analgesics to relieve the symptoms associated with teething. This study shows a common lack of knowledge about teething among parents. Parents should be better educated about the teething process and the proper management of teething troubles by the dental health care providers.


Fos expression in tyrosine hydroxylase containing hypothalamic neurons in CRH-KO mice: effect of immobilization stress.
Little is known about the response of tyrosine hydroxylase (TH) containing hypothalamic neurons to stress in corticoliberine deficient (CRH-KO) mice. This study was aimed to extend this issue and reveal the data leading to a better understanding of physiological/anatomical plasticity of hypothalamic TH cells in response to acute immobilization stress (IMO) as well as of possible of CRH body deficiency contribution in the regulation of TH cells during stress. We examined the topographic distribution of TH protein immunolabeled perikarya in selected hypothalamic structures including the paraventricular (PVN), supraoptic (SON), periventricular (PeVN), arcuate (ArcN), dorsomedial (DMN), and ventromedial (VMN) nuclei and extrahypothalamic zona incerta (ZI) in CRH-KO and wild type (WT) mice. The animals were perfused with fixative 120 min after a single IMO stress. The brains were removed, cryo-sectioned throughout the hypothalamus and Fos-TH co-localizations were processed immunohistochemically. Fos protein was visualized by diaminobenzidine (DAB) intensified with nickel ammonium sulphate, while TH cells were labeled only with DAB chromogen. The evaluation of Fos-TH co-labeled perikarya was performed with the use of computerized Leica light microscope and expressed as the percentage of total amount of TH labeled cells. From the qualitative point of view, the present data indicate similar anatomical distribution of TH immunoreactive perikarya in all brain structures investigated in both WT and CRH-KO mice, while from the quantitative point of view only TH cells in the DMN of CRH-KO mice showed a trend for increased activation by IMO. In several hypothalamic structures the basic population of TH neurons was not affected by the absence of endogenous CRH. Based on the data of this study it can also be assumed that despite of the presence of direct reciprocal connections between PVN and DMN neurons, PVN CRH neurons possibly are not participating in the regulation of TH neurons in the DMN during IMO stress. Hypothalamic nuclei - Fos-immunohistochemistry - Tyrosine hydroxylase - Immobilization stress - CRH knockout mice.


Increasing physical activity through health-enabling technologies: the project "being strong without violence".
Due to the increasing prevalence of adiposity in children numerous schools are introducing prevention programmes. Among these is "Gewaltlos Starksein" ("Being strong without violence"), a project of Hauptschule Sophienstraße Braunschweig, Germany (a general education secondary school for grades 5-10). This study aims to discover possible increases in activity through "Gewaltlos Starksein" where health-enabling technologies play a major role. A prospective intervention study with a span of 1.5 years was designed to measure this increase in activity. Partners in this study were Hauptschule Sophienstraße as the intervention group and Grund- und Hauptschule Pestalozzistraße as control group. Data collection was performed using a multi-sensor device, and questionnaires. Confirmatory data analysis of average metabolic equivalent (METs) yielded no significant results. Exploratory analysis showed interesting results, especially concerning the number of steps during leisure time. Descriptive analysis of questionnaires showed that all children enjoy physical activity. There were differences in sports team participation, open-air games and club affiliation. The study could not prove that the intervention "Gewaltlos Starksein" improves physical activity in children. However, the increased leisure activity step count indicates that "Gewaltlos Starksein" has positive effects on children's behaviour. This should be investigated in a further study in cooperation with psychologists.


[Efficacy observation of dysphagia after acute stroke treated with acupuncture and functional electric stimulation].
To observe the impacts on the recovery of swallowing function in patients of dysphagia after acute stroke treated with acupuncture and functional electric stimulation. Seventy-four patients were randomized into an acupuncture plus electric stimulation group (38 cases) and an electric stimulation group (36 cases). The functional electric stimulator was used in the two groups. The electric pads were placed on the hyoid bone, the upper part of thyroid cartilage, the masseter muscle and the mandibular joint. The treatment lasted for 30 mm each time. In the acupuncture plus electric stimulation group, acupuncture was supplemented at motor area of Jiao's scalp acupuncture, lower 2/5 of sensory area, Baihui (CV 20), Lianquan (CV 23), Jinjin (EX-HN 12) and Yuye (EX-HN 13), 30 mm each time. The treatment was given once a day, 6 treatments for one session and there was 1 day at interval between the sessions, 4 sessions were required totally in the two groups. The dysphagia scale was adopted for efficacy evaluation before treatment and after 4 sessions of treatment in the two groups. The removal rate of nasal feeding tube was observed after treatment. The dysphagia score was increased apparently after treatment compared with that before treatment in the two groups (both P < 0.05). After treatment, in the acupuncture plus electric stimulation group, the dysphagia score was increased much more apparently than that in the electric stimulation group (8.01 +/- 1.25 vs 6.73 +/- 1.36, P < 0.05). The remarkably effective rate was 84.2% (32/38) in the acupuncture plus electric stimulation group, better than 58.3% (21/36) in the electric stimulation group (P < 0.05). The removal rate of nasal feeding tube was 89.5% (34/38) in the acupuncture plus electric stimulation group, which was higher than 50. 0% (18/36) in the electric stimulation group (P < 0.05). Acupuncture combined with electric stimulation achieves the much better efficacy on dysphagia after acute stroke and promotes the early removal of nasal feeding tube. The efficacy is better than that of the simple electric stimulation therapy.


Exponential decay kinetics in "downhill" protein folding.
The observation of single-exponential kinetic phases in early stages of protein folding is often interpreted as evidence that these phases are rate limited by significant energy or entropy barriers. However, although the existence of large barriers reliably implies exponential kinetics, the reverse is not necessarily true. A simple model for the hydrophobic collapse of a chain molecule demonstrates that a barrierless or "downhill" diffusional relaxation can give rise to kinetics that are practically indistinguishable from a pure exponential. Within this model, even a highly nonlinear experimental probe such as resonance energy transfer (Förster transfer) could exhibit a large amplitude decay (greater than 90% in fluorescence) that deviates from a simple exponential by less than 0.5%. Only a detailed analysis of the dynamics is likely to reveal that a free energy barrier is absent.


Safety of anthrax vaccine: a review by the Anthrax Vaccine Expert Committee (AVEC) of adverse events reported to the Vaccine Adverse Event Reporting System (VAERS).
To assess the safety of a licensed anthrax vaccine given to nearly 400,000 US military personnel, reports of adverse events (AEs) submitted to the Vaccine Adverse Event Reporting System (VAERS) were reviewed and evaluated medically. The Anthrax Vaccine Expert Committee (AVEC), a civilian panel of private-sector physicians and other scientists, reviewed 602 VAERS reports using a Delphic approach (structured expert consensus) to assess the causal relationship between vaccination and the reported AEs and sought to identify unexpected patterns in the occurrence of medically important events. Reports were entered into a database and used to profile AEs with respect to person, type/location, relative frequency, severity/impact, concomitant illness or receipt of other drugs or vaccines, and vaccine lot. Nearly half the reports noted a local injection-site AE, with more than one-third of these involving a moderate to large degree of inflammation. Six events qualified as serious AEs (SAEs), and all were judged to be certain consequences of vaccination. Three-quarters of the reports cited a systemic AE (most common: flu-like symptoms, malaise, rash, arthralgia, headache), but only six individual medically important events were judged possibly or probably due to vaccine (aggravation of spondyloarthropathy (2), anaphylactoid reaction, arthritis (2), bronchiolitis obliterans organizing pneumonia). Since some cases of local inflammation involved distal paresthesia, AVEC recommends giving subcutaneous injections of AVA over the inferior deltoid instead of the triceps to avoid compression injury to the ulnar nerve. At this time, ongoing evaluation of VAERS reports does not suggest a high frequency or unusual pattern of serious or other medically important AEs.


Cardiopulmonary exercise testing in patients with asymptomatic left ventricular dysfunction: lack of prognostic predictive power of ventilatory variables.
The indication for cardiopulmonary exercise testing (CPET) in predictive evaluation has been extended beyond chronic heart failure (HF) patients to include asymptomatic left ventricular dysfunction (ALVD) patients, but its prognostic value is still unclear. We aimed to verify if CPET can predict outcome in ALVD and to identify which of the CPET parameters predictive in chronic HF are also effective in ALVD patients. We screened ALVD (LVEF ≤ 40% without HF symptoms) and HF patients for cardiac death, and compared peak oxygen consumption (pVO2), exertional oscillatory ventilation (EOV), and ventilatory response (VE/VCO2 slope) between survivors and non-survivors. Asymptomatic left ventricular dysfunction and HF patients formed the study population (585 ALVD and 695 HF). Both groups had similar male prevalence (98% vs. 98%; P = 0.345) but ALVD patients were younger (52 ± 10 vs. 60 ± 10 years, P = 0.004). Cardiac death was observed in 142 patients (5% of ALVD, 15% of HF). Exertional oscillatory ventilation occurred in 4% of ALVD, whereas VE/VCO2 slope was significantly lower (30 ± 7 vs. 35 ± 4) and pVO2 higher (16 ± 4 vs. 14 ± 3 mL/kg/min) than in chronic HF patients. Asymptomatic left ventricular dysfunction non-survivors had a significantly greater EOV incidence (13% vs. 3%, P = 0.003), lower pVO2 (13 ± 4 vs. 16 ± 3 mL/kg/min P = 0.000) and higher VE/VCO2 slope (33 ± 7 vs. 31 ± 5, P = 0.032). No ventilatory parameter had prognostic value at multivariable analysis in ALVD patients. Cardiopulmonary exercise testing can predict events in ALVD patients, but the risk stratification relies on different parameters than in HF patients. Further analysis in a multi-centre trial is required to better quantify the predictive impact of CPET risk parameters in ALVD patients.


Synergistic formulation approach for developing pea protein and guar gum enriched olive oil-in-water emulsion gels as solid fat substitutes: Formulation optimization, characterization, and molecular simulation.
This study aimed to optimize the formulation of olive oil-in-water (O/W) emulsion gels by incorporating Pea Protein (PP) and Guar Gum (GG) as alternative options for solid fats. The optimum rheological (consistency index, apparent viscosity, recovery) and texture (firmness) properties of the emulsion gels were obtained using a mixture of 2 % PP, 1 % GG, 60 % Olive Oil (OO), and 37 % Water (W). The blend of PP2/GG1 showed the highest results for recovery and firmness, 111.27 % and 33.89 g, respectively. PP/GG blend emulsion gels exhibited higher absolute ζ-potential values, ranging between -72.3 and -77.4 mV. The polydispersity index (PDI) ranged from 0.185 to 0.535, with the most uniform distributions found in the PP/GG blend emulsion gels. Strong phase separation resistance indicated strong stability of PP-GG complex emulsion gels. Higher PP concentrations decreased emulsion oxidation. FTIR and XRD research showed that PP and GG interact strongly, indicating good compatibility. The free binding energy of the most stable configuration of the molecules was -6.8 kcal mol-1, indicating a high affinity. PP interacted with GG through 9 amino acid residues, with notable residues being Asp 224, Thr 235, Ala 332, Ile 334, and Arg 336, and their respective interaction distances ranged between 2.69 Å and 3.87 Å.


Development of an LC/MS/MS method in order to determine arctigenin in rat plasma: its application to a pharmacokinetic study.
In this study, a simple and sensitive LC/MS/MS method was developed and validated for the determination of arctigenin in rat plasma. The MS detection was performed using multiple reaction monitoring at the transitions of m/z 373.2 → 137.3 for arctigenin and m/z 187.1 → 131.0 for psoralen (internal standard) with a Turbo IonSpray electrospray in positive mode. The calibration curves fitted a good linear relationship over the concentration range of 0.2-500 ng/mL. It was found that arctigenin is not stable enough at both room temperature and -80 °C unless mixed with methanol before storage. The validated LC/MS/MS method was successfully applied for the pharmacokinetic study of arctigenin in rats. After intravenous injection of 0.3 mg/kg arctigenin injection to rats, the maximum concentration, half-life and area under the concentration-time curve were 323 ± 65.2 ng/mL, 0.830 ± 0.166 and 81.0 ± 22.1 h ng/mL, respectively.


[The psychosocial factors associated with preschoolers' wellbeing in a kindergarten].
The aim of our investigation was to find out how do pre-school aged children felt themselves in kindergarten and what factors their well-being depended on. The survey was carried out in 1999 and 2000. A sample of 631 children aged 6-7 years was interviewed in 12 randomly selected kindergartens of Kaunas. The children were divided into two groups. The children who said that they liked to be in kindergarten more than at home belonged to the first group (n = 361 or 57.3%). They answered that they liked their group mates, like to speak with their teacher, to learn, to sing, to play quiet games, they heard good words about themselves in kindergarten more often. The children who enjoyed to be at home more than in kindergarten belonged to the second group (n = 269 or 42.7%). They said that they did not like to obey the tasks of their teacher, to sleep after dinner more often in comparison with the first group. Factorial analysis of the data indicated that children with positive factor of well-being through they were better than their group friends, thought they could do things better than their group mates, they had less complaints of various pains. A statistically significant correlation between the common factors of well-being and self-esteem was estimated.


Variations in pH sensitivity, acid stability, and fusogenicity of three influenza virus H3 subtypes.
Influenza A virus strains adapt to achieve successful entry into host species. Entry is mediated by the viral membrane protein hemagglutinin (HA), which triggers membrane fusion and genome release under acidic conditions in the endosome. In addition to changes in the receptor binding domain, the acid stability of HA has been linked to the successful transmission of virus between avian and human hosts. However, to fully understand the connection between changes in HA and host tropism, additional factors relevant to HA structure-function and membrane fusion are also likely to be important. Using single-particle-tracking (SPT) techniques, individual membrane fusion events can be observed under specific conditions, which provide detailed information regarding HA pH sensitivity and acid stability and the rate and extent of membrane fusion. This provides a comparative way to characterize and distinguish influenza virus fusion properties among virus strains. We used SPT to quantify the fusion properties of three H3 influenza strains: A/Aichi/68/H3N2 (X:31), A/Udorn/72/H3N2 (Udorn), and A/Brisbane/07/H3N2 (Brisbane). The rate of fusion for the most clinically relevant strain, Brisbane, is generally insensitive to decreasing pH, while the fusion of the egg-adapted strains Udorn and X:31 is strongly dependent on pH (and is faster) as the pH decreases. All strains exhibit similar acid stability (the length of time that they remain fusogenic in an acidic environment) at higher pHs, but the egg-adapted strains become less acid stable at lower pHs. Thus, it appears that the laboratory-adapted H3 strains tested may have evolved to compensate for the faster HA deactivation at low pH, with a commensurate increase in the rate of fusion and number of proteins facilitating fusion, relative to the Brisbane strain. The ability of influenza virus to release its genome under different acidic conditions has recently been linked to the transmission of influenza virus between different species. However, it is yet to be determined how acid-induced membrane fusion varies with virus strain and influences tropism. The results presented here are the results of an intra-H3-subtype study of acid stability and fusion kinetics. Using a single-particle-tracking (SPT) technique, we show here that the highest pH that initiates fusion is not necessarily the pH at which the kinetics of fusion is fastest and most abundant for a given strain. Strains exhibit different fusion behaviors, as evidenced by their unique kinetic trends; pH sensitivities, as evidenced by the differences when the first fusion events commence; and HA stabilities, as evidenced by the length of time that virions can persist in an acidic environment and still be fusion competent.