Effects of early postoperative mobilization following gastrointestinal surgery: systematic review and meta-analysis.
Early postoperative mobilization is considered a key element of enhanced recovery after surgery protocols. The aim of this study was to summarize the effect of early postoperative mobilization following gastrointestinal operations on patient recovery, mobility, the morbidity rate and duration of hospital stay. A systematic literature search was conducted in December, 2022, using PubMed, Web of Science and the Cochrane Central Register of Controlled Trials. Controlled trials reporting the effects of early postoperative mobilization after gastrointestinal surgery were included. The risk of bias was assessed using a modified Downs and Black tool and the Cochrane Collaboration tool for randomized trials. The outcomes of interest were gastrointestinal recovery (defined passage of first flatus or bowel movements), mobility (step count on postoperative day 3), the morbidity rate and duration of hospital stay. After elimination of duplicates, 3678 records were identified, and 71 full-text articles were screened. Finally, 15 studies (eight RCTs) reporting on 3538 patients were included. Most trials evaluated early postoperative mobilization after different gastrointestinal operations, including upper gastrointestinal (n = 8 studies), hepatopancreatobiliary (n = 10 studies) and colorectal resections (n = 10 studies). The investigated early postoperative mobilization protocols, operative techniques (minimally invasive or open) and outcome parameters were heterogeneous between the studies. Early postoperative mobilization seemed to significantly accelerate clinical gastrointestinal recovery (mean difference, hours: -11.53 (-22.08, -0.97), P = 0.03). However, early postoperative mobilization did not significantly improve the morbidity rate (risk ratio: 0.93 (0.70, 1.23), P = 0.59), postoperative mobility of patients (step count mean difference: 1009 (-803, 2821), P = 0.28) or shorten the duration of hospital stay (mean difference, days: -0.25 (-0.99,0.43), P = 0.47) in randomized trials. There is a large heterogeneity among the study cohorts, operations and interventions. The available evidence currently does not support specific early postoperative mobilization protocols as an isolated element to further reduce the morbidity rate and duration of hospital stay. Further well-designed trials are required to identify effective early postoperative mobilization protocols.


Long-Term Plastic Greenhouse Cultivation Changes Soil Microbial Community Structures: A Case Study.
Plastic greenhouse vegetable cultivation (PGVC) has been widely developed around the world and has resulted in great changes in soil properties and potential contamination by phthalate esters (PAEs). Using high-throughput sequencing, this study investigated the succession and potential factors impacting soil microbial community structures over 20 years of PGVC. The results showed that the pH of soils under PGVC were significantly lower, while the nutrient contents of soils were higher, relative to those of open field soil. The residue concentrations of PAEs in soil under PGVC increased with increasing periods of PGVC. The fungal community diversity, rather than the bacterial community diversity, was significantly reduced in soils under PGVC. However, both the soil bacterial and fungal community structures were changed by long-term PGVC. Among the tested soil physicochemical properties, soil pH and clay were the top two factors affecting the soil bacterial community, while pH and phosphorus (P) mainly affected the soil fungal community structures. No relationship between the changes of microbial communities and PAE residues in soil was observed. This study indicates that the soil acidification and nutrient accumulation under PGVC mainly shifted the changes of soil microbial community structures, which could occur after only 5 years of PGVC.


Molecular cloning of Mu d(bla lacZ) transcriptional and translational fusions.
The vector pBW2 was made to selectively clone chimeric plasmids with chromosomal Mu d(bla lacZ) transcriptional or translational fusions. It was tetracycline resistant and had the carboxyl-terminal end of bla distal to its PstI site. Because ligation of PstI-digested chromosomal DNA of a Mu d(bla lacZ) insertion with pBW2 restored bla, ampicillin-resistant chimeric plasmids were selectable. These plasmids had the Mu d bla amino terminus and simultaneously acquired other Mu d sequences including lacZ, the chromosomal fusion joint, and the DNA adjacent to the nearest chromosomal PstI site. The plasmid pBW2 was useful in the molecular cloning of several psi and pho::lacZ(Mu d) fusions, as well as chromosomal genes located near Mu d insertions.


Efficacy comparison of multiple-antigen subcutaneous injection immunotherapy and multiple-antigen sublingual immunotherapy.
We performed an observational study to determine whether allergen-specific sublingual immunotherapy (SLIT) is as effective as allergen-specific subcutaneous injection immunotherapy (SCIT). Our study population was comprised of 66 patients who had been taking SLIT. Of this group, 36 patients had switched to SLIT after having been treated with SCIT (group I), while the remaining 30 patients had received SLIT only (group II). A questionnaire was used to evaluate the results of treatment. In group I, 33 patients (92%) gave SLIT a favorable rating; 27 of these patients (75%) said it was just as effective as SCIT and 6 (17%) said it was actually superior(the remaining 3 patients [8%] said that SCIT was better). In group II, 27 of 30 patients (90%) said they had attained symptom relief with SLIT; 21 (70%) said that the relief had been very significant. Overall, 60 of the 66 patients (91%) expressed various degrees of satisfaction with SLIT We believe that our SLIT protocol, which is based on established guidelines for SCIT administration, is an effective, safe, well-tolerated, and easy-to-use regimen. Future prospective studies of larger groups are clearly indicated.


Physicochemical Characterization of Novel Biomaterial Consisting of Biphasic Calcium Phosphate, Chitosan, Casein and Ethanolic Leaves Extract of Ormocarpum Cochinchinense.
Bioceramics are widely used as a biomaterial to promote bone regeneration. Bone defect management requires the placement of bone grafts. Though there are many bone grafts available, these have certain limitations like limited supply and second surgical site morbidity. Phytochemicals in plants are known to have bone regeneration capacity and are used in traditional medicine for bone fracture healing. The purpose of the study was to create a novel biomaterial consisting of a composite of biphasic calcium phosphate (BCP), chitosan (CH), casein (CA), and ethanolic leaves extract of Ormocarpum Cochinchinense (OC) fabricated and characterized for physicochemical properties. BCP-CH-CA-OC material was prepared and immersed in Simulated body fluid (SBF) for 21 days. Physical properties were analysed through X-Ray diffraction (XRD), Fourier Transform Spectroscopy (FTIR), and Scanning Electron Microscopy with Energy dispersion spectroscopy (SEM/EDS). Mechanical properties were analysed by compressive strength and diametral tensile strength tests. Using BET (Brunauer-Emmett-Teller) analysis and Nano computed tomography (CT) scan, porosity measurements were made. XRD did not show any significant change after immersion in SBF, indicating that the material was not under change and is stable. FTIR showed an increase in chitosan content, due to the loss of casein. SEM analysis showed the deposition of crystals and porous structure. EDS showed the deposition of minerals. Nano CT and BET analysis showed clinically significant porosity of 30%. The mechanical and physical properties of this novel biomaterial could be used in tissue engineering for the repair of bone defects in non-load-bearing areas. The physicochemical properties are at par with other materials used for the purpose of bone grafting. The novel biomaterial has the potential to be used in bone regenerative medicine in non-load-bearing applications.


An ELISA for recombinant Lepidoglyphus destructor, Lep d 2, and the monitoring of exposure to dust mite allergens in farming households.
Exposure to indoor allergens, such as dust mites, has been recognized as a risk factor for sensitization and symptoms. To develop a two-site ELISA for the determination of Lep d 2 in the reservoir, to measure dust mite allergen exposure (Lep d 2, Der p 1, Der f 1 and Der 2) in farm households, and to investigate whether exposure to these allergens is associated with sensitization, asthma and rhinoconjunctivitis. Monoclonal antibodies to recombinant (r)Lep d 2 were produced with standard hybridoma technique. Dust samples from 393 households were analysed for allergen content by two-site ELISA methods. A two-site Lep d 2 ELISA was developed with a detection limit of 0.09 microg/g. The assay was highly reproducible and levels of Lep d 2 showed a strong correlation with the number of Lepidoglyphus mites (r(s): 0.7; P = 0.0002). Lep d 2 was detected in 20% of the homes; levels ranged from 0.09 to 1.7 microg/g of dust. Der p 1 was recorded in 59% of the samples, ranging from 0.055 to 139 microg/g, and Der f 1 and Der 2 in 40% and 50% of the samples, ranging from 0.055 to 24.5 microg/g and 24.3 microg/g, respectively. Dermatophagoides allergens were significantly higher in mattresses than in carpets (P < 0.0001), but this difference was not observed with Lep d 2. A strong relationship between immunoglobulin (Ig)E to rLep d 2 and asthma (OR = 10.4) and rhinoconjunctivitis (OR = 7.5) was seen. Furthermore, sensitization to D. pteronyssinus was significantly associated with asthma (OR: 13.7) and rhinoconjunctivitis (OR: 5.7). When assessing mite allergen exposure in rural homes, not only the Der p 1, Der f 1 and Der 2 allergens, but also the Lep d 2 allergen should be taken into consideration.


A Comparative Evaluation of ELISA, PCR, and Serum Agglutination Tests For Diagnosis of Brucella Using Human Serum.
Since the symptoms of Brucellosis are often atypical and nonspecific, using clinical signs alone to diagnose brucellosis is not advised; therefore, the diagnosis relies predominantly on laboratory testing. Currently, molecular, serological, and microbiological methods are used for diagnosis of this disease. In this study we examined ELISA, PCR and serum agglutination (SAT) methods on human patient serum samples. A total of 100 serum samples were collected from suspected patients. Fifty serum samples gave a positive result with the Wright test. The ELISA method was first employed on all samples for the detection of IgG and IgM antibodies against Brucella. Subsequently, the rapid PCR methodology was used to identify presence of Brucella genome in 500 µL of each serum sample. The B4/B5 primer pair was used for PCR amplification. Out of the 100 serum samples obtained from patients with suspected brucellosis, 50 samples tested positive by SAT and displayed high titers of 1/160. Of these 50 positive samples, 49 samples were positive as per the ELISA test whereas one sample tested negative. The PCR test was conducted on all 100 serum samples and results showed that the 45 serum samples that gave a positive agglutination test were also positive by PCR. Various laboratory methods have been used or introduced for the detection of Brucella. Molecular methods such as PCR, a rapid and sensitive method for detection of bacteria, have also been reported. Based on the results of this study, we propose that the simultaneous use of serology and molecular techniques has the potential to overcome limitations of detection thereby enabling the selection of appropriate treatment for the patient.


Mechanical and electrical properties of carbon nanotube/Cu nanocomposites by molecular-level mixing and controlled oxidation process.
A molecular-level mixing and controlled oxidation process is proposed as a novel fabrication technique for the production of CNT/Cu nanocomposite powders. The fabricated CNT/Cu2O nanocomposite powders showed microstructures with homogeneous dispersion of implanted CNTs in a Cu2O matrix. The CNT/Cu2O nanocomposite powders were reduced to CNT/Cu nanocomposite powders with H2 gas and then the as-prepared CNT/Cu nanocomposite powders were spark plasma sintered to fabricate CNT/Cu nanocomposites. The mechanical properties of the Cu and the CNT/Cu nanocomposites were characterized by tensile testing before and after hot compression. Before hot compression, the CNT/Cu nanocomposites were brittle, but after hot compression both yield strength and elongation were increased, while the yield strength of the Cu was decreased after hot compression. Hot compression enhanced the ductility and strength of the CNT/Cu nanocomposites due to alignment of Cu grains and CNTs. Electrical conductivity was also enhanced due to a reduced scattering of electrons because of the alignment of the CNTs and Cu grains as well as the annealing effects of the Cu matrix.


Bone lineage proteins in the entheses of the midfoot in patients with spondyloarthritis.
Patients with juvenile-onset spondyloarthritis (SpA) may develop ankylosis of the midfoot resembling the spinal changes seen in patients with ankylosing spondylitis (AS). The study of the histopathology of the feet of patients with tarsitis could help us understand the pathogenesis of bone formation in affected structures in the SpA. The objective of our study was to describe the histopathologic characteristics of the midfoot in patients with tarsitis associated with SpA. We obtained synovial sheaths, entheses, and bone samples from 20 patients with SpA with midfoot pain/tenderness and swelling. Tissue samples underwent H&E staining; immunohistochemistry for CD3, CD4, CD8, CD68, and CD20 cell identification; and immunofluorescence for bone lineage proteins, including osteocalcin, osteopontin, parathyroid hormone-related protein, bone sialoprotein, and alkaline phosphatase. Slight edema and hyalinization were found in some tendon sheaths, and few inflammatory cells were detected in the entheses. In bones, we found some changes suggesting osteoproliferation, including endochondral and intramembranous ossification, but no inflammatory cells. In entheses showing bone proliferation, we detected osteocalcin and osteopontin in cells with a fibroblast-mesenchymal phenotype, suggesting the induction of entheseal cells toward an osteoblast phenotype. Osteoproliferation and abnormal expression of bone lineage proteins, but no inflammatory infiltration, characterize midfoot involvement in patients with SpA. In this sense, tarsitis (or ankylosing tarsitis) resembles the involvement of the spine in patients with AS. Ossification may be in part explained by the differentiation of mesenchymal entheseal cells toward the osteoblastic lineage.


Cardiac output during exercise is related to plasma atrial natriuretic peptide but not to central venous pressure in humans.
What is the central question of this study? Is cardiac output during exercise dependent on central venous pressure? What is the main finding and its importance? The increase in cardiac output during both rowing and running is related to preload to the heart, as indicated by plasma atrial natriuretic peptide, but unrelated to central venous pressure. The results indicate that in upright humans, central venous pressure reflects the gravitational influence on central venous blood rather than preload to the heart. We evaluated the increase in cardiac output (CO) during exercise in relationship to central venous pressure (CVP) and plasma arterial natriuretic peptide (ANP) as expressions of preload to the heart. Seven healthy subjects (four men; mean ± SD: age 26 ± 3 years, height 181± 8 cm and weight 76 ± 11 kg;) rested in sitting and standing positions (in randomized order) and then rowed and ran at submaximal workloads. The CVP was recorded, CO (Modelflow) calculated and arterial plasma ANP determined by radioimmunoassay. While sitting, (mean ± SD) CO was 6.2 ± 1.6 l min-1 , plasma ANP 70 ± 10 pg ml-1 and CVP 1.8 ± 1.1 mmHg, and when standing decreased to 5.9 ± 1.0 l min-1 , 63 ± 10 pg ml-1 and -3.8 ± 1.2 mmHg, respectively (P < 0.05). Ergometer rowing elicited an increase in CO to 22.5 ± 5.5 l min-1 as plasma ANP increased to 156 ± 11 pg ml-1 and CVP to 3.8 ± 0.9 mmHg (P < 0.05). Likewise, CO increased to 23.5 ± 6.0 l min-1 during running, albeit with a smaller (P < 0.05) increase in plasma ANP, but with little change in CVP (-0.9 ± 0.4 mmHg). The increase in CO in response to exercise is related to preload to the heart, as indicated by plasma ANP, but unrelated to CVP. The results indicate that in upright humans, CVP reflects the gravitational influence on central venous blood rather than preload to the heart.


Influence of bacteriophage preparations on intracellular killing of bacteria by human phagocytes in vitro.
Bacteriophages are viruses that infect bacteria. It was shown that bacteriophage therapy is an effective method of combating bacterial infections, including infections caused by antibiotic-resistant bacterial strains. One of the main obstacles to widespread use of phage preparations is limited knowledge regarding the influence of bacteriophages on human organisms. In our study, we evaluated whether application of phage preparations impair bactericidal activities of human phagocytes (granulocytes and monocytes). In our study, we used preparations of phages T2 and T4 specific to Escherichia coli and A3 phage specific to Staphylococcus aureus. We found that bacteriophage preparations do not influence intracellular killing of bacteria by human phagocytes. The effect is irrespective of phage preparation type (lysate, purified phage preparation), phage titer of the preparation, and whether bacteria phagocytosed by phagocyte cells are sensitive or insensitive to phage (bacteriophages homologous and heterologous to bacteria). Although the results of our study are preliminary, they support previous data indicating safety of therapeutic application of phages.


[Immunocytochemical studies on the phase of differentiation of hatching gland cells in brine shrimp, Artemia salina].
Hatching enzyme (HE), synthesized in hatching gland cells (HGCs), plays vital roles in animal hatching. Immunocytochemical techniques employing anti-GST-UVS.2 antiserum, prepared from Xenopus HE and with specificity to brine shrimp HE, were first used to investigate the differentiation and variability of hatching gland cells (HGCs) in the hatching process of embryos of brine shrimp, Artemia salina, in this study. HGCs with immunoreactivity to anti-GST-UVS.2 antiserum were identified, for the first time, in brine shrimp embryos during hatching process. Immunocytochemical staining results showed that, (1) HE-positive immunoreactivity is really specific to Artemia HE, and its appearance and disappearance are closely correlated with the hatching process of Artemia salina. (2) Artemia HGCs, first appeared in embryos 5 hours before hatching and disappeared 4 hours after hatching, were also a transient type of cells, with an existence period of 9 hours. (3) The head portion of Artemia embryo is probably the initial position of HE secretion, and likely to be the main position of HE secretion as well. The detailed process and mechanism need to be studied. (4) The appearance of HGCs is in a synchronous mode from places all over the embryos, and their disappearance is also in a synchronous mode. (5) The number of HGCs increased gradually along with embryo development process and reached a maximum number at hatching. Contrarily, the number of HGCs decreased gradually after hatching, and HGCs disappeared 5 hours after hatching. However, the intensity of HE-positive reaction was almost at the same level at the period of HGCs'presence. (6) Artemia HGCs were distributed throughout the body of embryos at all time during their presence. Therefore, it can concluded that Artemia HGCs, as a transient type of cells, first appeared in embryos 4 hours before hatching and disappeared in embryos 5 hours after hatching, and with distinguished patterns of appearance, disappearance and distribution in embryos. What is the final destiny of Artemia HGCs after hatching? And what is the biological significance of remanet HGCs, still existing until 4 hours after hatching, in fresh-hatched Artemia larvae? Is it possible that the HGCs are involved in larvae yolk digestion? Moreover, what is the molecular mechanism of HGCs' synchronous sudden appearance and disappearance? All these questions remain to be further studied and approved.


Systematic review of community health impacts of mountaintop removal mining.
The objective of this evaluation is to understand the human health impacts of mountaintop removal (MTR) mining, the major method of coal mining in and around Central Appalachia. MTR mining impacts the air, water, and soil and raises concerns about potential adverse health effects in neighboring communities; exposures associated with MTR mining include particulate matter (PM), polycyclic aromatic hydrocarbons (PAHs), metals, hydrogen sulfide, and other recognized harmful substances. A systematic review was conducted of published studies of MTR mining and community health, occupational studies of MTR mining, and any available animal and in vitro experimental studies investigating the effects of exposures to MTR-mining-related chemical mixtures. Six databases (Embase, PsycINFO, PubMed, Scopus, Toxline, and Web of Science) were searched with customized terms, and no restrictions on publication year or language, through October 27, 2016. The eligibility criteria included all human population studies and animal models of human health, direct and indirect measures of MTR-mining exposure, any health-related effect or change in physiological response, and any study design type. Risk of bias was assessed for observational and experimental studies using an approach developed by the National Toxicology Program (NTP) Office of Health Assessment and Translation (OHAT). To provide context for these health effects, a summary of the exposure literature is included that focuses on describing findings for outdoor air, indoor air, and drinking water. From a literature search capturing 3088 studies, 33 human studies (29 community, four occupational), four experimental studies (two in rat, one in vitro and in mice, one in C. elegans), and 58 MTR mining exposure studies were identified. A number of health findings were reported in observational human studies, including cardiopulmonary effects, mortality, and birth defects. However, concerns for risk of bias were identified, especially with respect to exposure characterization, accounting for confounding variables (such as socioeconomic status), and methods used to assess health outcomes. Typically, exposure was assessed by proximity of residence or hospital to coal mining or production level at the county level. In addition, assessing the consistency of findings was challenging because separate publications likely included overlapping case and comparison groups. For example, 11 studies of mortality were conducted with most reporting higher rates associated with coal mining, but many of these relied on the same national datasets and were unable to consider individual-level contributors to mortality such as poor socioeconomic status or smoking. Two studies of adult rats reported impaired microvascular and cardiac mitochondrial function after intratracheal exposure to PM from MTR-mining sites. Exposures associated with MTR mining included reports of PM levels that sometimes exceeded Environmental Protection Agency (EPA) standards; higher levels of dust, trace metals, hydrogen sulfide gas; and a report of increased public drinking water violations. This systematic review could not reach conclusions on community health effects of MTR mining because of the strong potential for bias in the current body of human literature. Improved characterization of exposures by future community health studies and further study of the effects of MTR mining chemical mixtures in experimental models will be critical to determining health risks of MTR mining to communities. Without such work, uncertainty will remain regarding the impact of these practices on the health of the people who breathe the air and drink the water affected by MTR mining.


Production of cytokeratin 19 fragment by human squamous lung cancer cell lines.
Cytokeratins form part of the cytoskeleton of both normal and malignant epithelium. A novel tumor marker measuring cytokeratin 19 (CK-19) fragment has been introduced and proven to be suitable for monitoring therapy and following cases of non-small cell lung cancer, squamous cell lung cancer in particular. However, whether the serum level of CK-19 fragment reflects the number of proliferating tumor mass remains unknown. We studied the CK-19 fragment produced by two human squamous cell lung cancer cell lines. In Western blotting analysis, culture supernatants of both cell lines displayed bands of 37 and 40 kDa, which represented the CK-19 fragment and the intact CK-19, respectively. Gel filtration demonstrated that a part of soluble CK-19 was released as a large complex form in culture supernatants. The level of CK-19 fragment in culture supernatants increased during the exponential growth phase. CK-19 level decreased by an addition of a cytotoxic agent to non-significant level though the transient release of CK-19 fragment occurred during the first 2 days. After all, soluble CK-19 fragments were detected in culture supernatants of human lung cancer cell lines and its level reflected proliferating cancer cells though it was not determined whether CK-19 fragments were released directly from live cells.


Forward and robust selection of the most potent and noncellular toxic siRNAs from RNAi libraries.
Use of highly potent small interfering RNAs (siRNAs) can substantially reduce dose-dependent cytotoxic and off-target effects. We developed a genetic forward approach by fusing the cytosine deaminase gene with targets for the robust identification of highly potent siRNAs from RNA interference (RNAi) libraries that were directly delivered into cells via bacterial invasion. We demonstrated that two simple drug selection cycles performed conveniently in a single container predominately enriched two siRNAs targets the MVP gene (siMVP) and one siRNA targets the egfp gene (siEGFP) in surviving cells and these proved to be the most effective siRNAs reported. Furthermore, the potent siRNAs isolated from the surviving cells possessed noncellular toxic characteristics. Interestingly, the length of highly potent siMVPs identified could be as short as 16-mer, and increasing the length of their native sequences dramatically reduced RNAi potency. These results suggest that the current approach can robustly discover the most potent and nontoxic siRNAs in the surviving cells, and thus has great potential in facilitating RNAi applications by minimizing the dose-dependent and sequence nonspecific side effects of siRNAs.


Overexpression of PIN1 Enhances Cancer Growth and Aggressiveness with Cyclin D1 Induction in EBV-Associated Nasopharyngeal Carcinoma.
Nasopharyngeal carcinoma (NPC) is a peculiar Epstein Barr virus (EBV)-associated malignancy that is prevalent in South-East Asia. Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) isomerizes specific phosphorylated amino acid residues, which makes it an important regulator in cell survival and apoptosis. In this study, we investigated the contribution made by PIN1 in NPC tumorigenesis and PIN1's potential role as a therapeutic target. The expression of PIN1 was examined in a panel of NPC cell lines, xenografts and primary tumors. The functional roles of PIN1 in NPC cells were elucidated by the knockdown and overexpression of PIN1 in in vitro and in vivo nude mice models by siRNA and lenti-viral transfection, respectively. The antitumor effects of the PIN1 inhibitor Juglone in NPC cells were also evaluated. We revealed the consistent overexpression of PIN1 in almost all EBV-associated NPC cell lines, xenografts and primary tumors. PIN1 suppression was capable of inhibiting cyclin D1 expression and activating caspase-3 in NPC cells. It positively regulated NPC cell proliferation, colony formation and anchorage-independent growth. The inhibition of PIN1 suppressed tumor growth in vitro and in vivo. This study demonstrates the oncogenic role of PIN1 in NPC tumorigenesis, and shows that its overexpression can enhance tumor cell growth via the upregulation of cyclinD1. Our findings inform the development of novel treatments targeting PIN1 for NPC patients.


Are We Overdiagnosing Acute Kidney Injury in Pediatric Patients Following Cardiac Surgery?
The use of two diagnostic criteria in the current literature has led to some degree of ambiguity in the precise diagnosis of acute kidney injury in pediatric patients undergoing surgery for congenital heart disease. This study aims to determine which criteria is the most accurate diagnostic indicator of acute kidney injury and determine whether the incidence is being overestimated based on the current criteria. This retrospective study consisted of 389 patients with congenital heart disease from birth to 18 years, who underwent cardiac surgery. The statistical tests conducted were the student t test and chi-square test. Outcomes measured included hospital length of stay, duration of mechanical ventilation, and mortality. The incidence rate of acute kidney injury diagnosed by the pediatric Risk, Injury, Failure, Loss, and End-Stage Renal Disease (RIFLE) criterion was 56% compared to 24.4% for the Acute Kidney Injury Network criterion. The pediatric RIFLE criterion consists of the following subsets: risk, injury, failure, loss, and end-stage renal disease. Patients classified in the "risk" subset of the pediatric RIFLE criterion who failed to meet Acute Kidney Injury Network criterion were compared to patients without acute kidney injury. Comparison of intensive care unit outcomes between these groups lacked statistical significance for all variables except the duration of mechanical ventilation postoperatively. Although recent research in this field identified the pediatric RIFLE criterion as the most sensitive indicator of acute kidney injury, the results of this study suggest the pediatric RIFLE criterion overestimates acute kidney injury incidence and that the Acute Kidney Injury Network criterion is the more accurate diagnostic indicator.


Coarse-graining scheme for simulating uniaxial stress-strain response of glassy polymers through molecular dynamics.
Simulation of the deformation of polymers below their glass transition through molecular dynamics provides an useful route to correlate their molecular architecture to deformation behavior. However, present computational capabilities severely restrict the time and length scales that can be simulated when detailed models of these macromolecules are used. Coarse-graining techniques for macromolecular structures intend to make bigger and longer simulations possible by grouping atoms into superatoms and devising ways of determining reasonable force fields for the superatoms in a manner that retains essential macromolecular features relevant to the process under study but jettisons unnecessary details. In this work we systematically develop a coarse-graining scheme aimed at simulating uniaxial stress-strain behavior of polymers below their glass transition. The scheme involves a two step process of obtaining the coarse grained force field parameters above glass transition. This seems to be enough to obtain "faithful" stress-strain responses after quenching to below the glass transition temperature. We apply the scheme developed to a commercially important polymer polystyrene, derive its complete force field parameters and thus demonstrate the effectiveness of the technique.


A theoretical and clinical perspective of an embodied view in psychotherapy of somatic symptoms disorders.
In this paper, we offer some ideas for the treatment of somatoform patients and related pathologies based on the concept of embodiment. Embodiment refers to the interplay between body and mind in behavior. The word refers to giving a body to something, "incarnate". Spinoza wrote extensively about the topic in the 17th century. In the 20th century, picking up on Spinoza's work, Damasio presented extensive and important neuro-scientific evidence that feelings can be direct perceptions of internal body states, substantiating the growing understanding of emotions and feelings as a core component of the embodied experience. Here, we summarize the evidence for the intersection of emotion and cognition in the body, which impinges on the effectiveness of using the body and movement in psychotherapy and the management of somatic symptoms and related disorders. We present evidence indicating that movement would be a way to reach unconscious processes dealing with body-mind interaction and body awareness.


Institutional response to FDA warning on aprotinin and impact on outcomes.
New evidence of potential risks of aprotinin in 2006 generated public concern about a previously approved drug that was routinely used. In response, we assembled a team of experts within the institution to form guidelines for the appropriate use of aprotinin in cardiac surgery. We report the basis for the guidelines, their implementation, follow-up and resulting patterns of change in aprotinin use. We proposed a three-tier system for aprotinin use, according to risk of bleeding and transfusion, and evidence of benefit of aprotinin. Specific recommendations were made with regard to discussion with the patient and documentation regarding aprotinin use and options for patients who refuse the drug. Guidelines were disseminated and accessible on all anesthesia workstations. Aprotinin use was compared before and after institution of guidelines in equivalent categories. Aprotinin was used in 58.5% (469/802) of cases from March 2005 to January 2006. Following institution of guidelines from March 2006 to January 2007, aprotinin was used in 19.7% (151/767) cases representing a 67.8% reduction in usage. In the subset of groups with large reductions in aprotinin use (pre- 82%, n=239; post-guidelines 17%, n=241) there was a significant decrease in acute kidney injury (%?Cr 43.8 vs. 31.7%, p=0.05). In response to new data and regulatory guidelines, we formulated guidelines based on expert review of data. We reduced aprotinin use, but more importantly, introduced an evidence-based approach to the use of aprotinin, consistent with regulatory guidelines. This model of guideline implementation can be useful in similar scenarios.


Redescription of Neotyphloceras crassispina hemisus Jordan (Siphonaptera: Ctenophthalmidae: Neotyphloceratini).
Neotyphloceras crassispina hemisus Jordan is redescribed from male and female specimens collected at the type locality (Otro Cerro, Catamarca Province, Argentina) and nearby localities. New diagnostic morphological characters for both sexes are provided, which include the shape of the upper lobe of the fixed process of clasper, the crochet of the aedeagus and the shape and chaetotaxy of the distal arm of sternum IX for males, and the contour of the distal margin of sternum VII for females.


The hybrid bio-inspired aerial vehicle: Concept and SIMSCAPE flight simulation.
This paper introduces a Silver Gull-inspired hybrid aerial vehicle, the Super Sydney Silver Gull (SSSG), which is able to vary its structure, under different manoeuvre requirements, to implement three flight modes: the flapping wing flight, the fixed wing flight, and the quadcopter flight (the rotary wing flight of Unmanned Air Vehicle). Specifically, through proper mechanism design and flight mode transition, the SSSG can imitate the Silver Gull's flight gesture during flapping flight, save power consuming by switching to the fixed wing flight mode during long-range cruising, and hover at targeted area when transferring to quadcopter flight mode. Based on the aerodynamic models, the Simscape, a product of MathWorks, is used to simulate and analyse the performance of the SSSG's flight modes. The entity simulation results indicate that the created SSSG's 3D model is feasible and ready to be manufactured for further flight tests.


NANOGP8 expression regulates gastric cancer cell progression by transactivating DBC1 in gastric cancer MKN-45 cells.
NANOGP8 is one of the NANOG pseudogenes and is expressed together with NANOG in multiple tumor tissues and cell lines. The biological functions of NANOGP8 in progression of gastric cancer are unclear. In the present study, the role of NANOGP8 was investigated in gastric cancer cells. The gathered data demonstrated that NANOG expression in both mRNA and protein was elevated in gastric cancer cell lines relative to a normal gastric epithelial cell line. Downregulation of NANOGP8 inhibited cell proliferation and increased apoptosis in human gastric carcinoma cell lines. Furthermore, silencing of NANOGP8 suppressed tumor growth in vivo. Interestingly, it was identified that deleted in breast cancer 1 (DBC1) expression was also markedly downregulated following NANOGP8 knockdown. DNA microarray and dual-luciferase assays further indicated that NANOGP8 may bind to the DBC1 promoter region and regulate DBC1 expression. Therefore, the gathered data provided evidence that NANOGP8 contributes to progression of gastric cancer via DBC1 and may have potential translational significance.


Spatial Multiplexing of Whispering Gallery Mode Sensors.
Whispering gallery mode resonators have proven to be robust and sensitive platforms for the trace detection of chemical and/or biological analytes. Conventional approaches using serially addressed resonators face challenges in simultaneous multi-channel (i.e., multi-species) detection. We present an alternative monitoring scheme that allows for the spatial multiplexing of whispering gallery mode resonators with the simultaneous observation of the resonance spectra from each of them. By imaging arrays of microspheres and monitoring the glare spot intensities through image processing routines, resonance spectra from multiple resonators may be simultaneously recorded without interference or confounding effects of serial excitation/detection. We demonstrate our multiplexed imaging approach with bulk refractive index variations and virus-antibody binding.


A retrospective study of nonneoplastic and neoplastic disorders of the salivary glands.
The spectrum of major and minor salivary gland disorders varies widely. Epidemiological data on some injury categories are rare and often not up-to-date. This study aims to analyze epidemiological data using clinical, paraclinical, and histopathological parameters. Study was carried out for 5 years on the nonneoplastic and tumoral pathology of the salivary glands. Data were statistically analyzed using the appropriate parameters. Data analysis according to the biological behavior of the lesions revealed great heterogeneity. Statistically significant correlations were observed between the type of injury, age (P = .002) and gender (0.033). The environment of origin of the patients as well as the comorbidities reflected in most cases the nature of the process. Associations were also observed between the biological behavior of the lesions and the hemicranial topography (P = .019), the type of salivary gland (P = .024), and the surgical technique used (P < .001). Most cases were identified in the major salivary glands, often in the parotid. The most common diseases are represented by nonspecific chronic sialadenitis (nonneoplastic lesion), pleomorphic adenoma and Warthin tumor (benign tumors), mucoepidermoid carcinoma (malignant tumor), and squamous carcinoma (secondary tumor). They presented axial diameters between 2 to 95 mm. The most used curative technique was subtotal excision with facial nerve preservation. In conclusion, the study highlighted the main epidemiological aspects of salivary gland disorders. Some data agree with the specialty literature, and particular aspects are also observed. Therefore, this research is useful both in the medical and research fields.


Novel markers of COVID-19 mortality-A comparative study with patients of acute coronary syndrome.
COVID-19 can cause severe pneumonia that can progress to multiple organ failure. It is believed that dysregulation of inflammation and cytokine storm, contributes to severe COVID-19. As inflammatory mediators play an important role in the pathogenesis of the severe disease, inflammatory markers like fever, leucocytosis, and C-reactive protein are known to predict severe disease. Various other biomarkers have been known to have prognostic value in patients with COVID-19 infection. Inflammation, both local and systemic plays an important role in the pathogenesis of acute coronary syndrome (ACS). Thus in this study, we aimed to compare and describe the various biomarkers, and mortality between patients admitted with COVID-19 infection and ACS patients without COVID-19 infection. In a retrospective observational case-control study, a total of 108 patients admitted to our hospital during the month of May 2021 with COVID-19 were enrolled. Patients of the acute coronary syndrome (tested negative for COVID-19 infection) admitted during the same month were enrolled (including both the intensive care unit and ward) as controls. The median age of patients with COVID was significantly lower than that of patients with acute coronary syndrome [49 years (IQR, 36-62 years) and 60 years (IQR, 52-66 years)]. Left ventricular ejection fraction was significantly higher among patients with COVID infection (58.5 ± 6.3% versus 36.9 ± 9.3%). The total leukocyte count was significantly higher among patients with COVID-19 compared to those with acute coronary syndrome [13200 per microliter (8625-17500) vs 9800 per microliter (8150-12150), P < 0.001]. The blood urea level was significantly higher among patients with COVID infection [52.5 (IQR, 34.7-81.5) versus 20 (IQR, 16-31)]. Levels of C-reactive protein were significantly higher among patients with COVID [39 (IQR, 7.7-100) versus 2 (1.4-3.5)]. The mortality of patients hospitalized with COVID was 4 times higher than those with acute coronary syndrome [25.9% (28) versus 6.1% (6)]. Survivors of COVID-19 had higher hemoglobin levels than those who did not [12.5 g/dLvs 11.5 g/dL, P = 0.03]. Elevated total leukocyte counts reflect underlying secondary bacterial infection among patients with COVID-19 and help initiate appropriate antibiotics. Depletion of intravascular volume reflected by an increased urea/creatinine ratio increases the risk of mortality and warrants aggressive measures of rehydration and albumin infusion.


COP1 is downregulated in renal cell carcinoma (RCC) and inhibits the migration of RCC ACHN cells in vitro.
Constitutive photomorphogenic 1 (COP1) belongs to the COP‑de-etiolated (DET)‑fusca (FUS) protein family and has been demonstrated to suppress prostate adenocarcinomas and other types of tumor, such as liver and gastric cancer. The present study investigated the expression of COP1 and its downstream factor, ets variant 1 (ETV1) in renal cell carcinoma (RCC) tissue samples, and evaluated the correlation of COP1 expression levels with the clinicopathological characteristics of RCC. In addition, the role of COP1 in the proliferation and migration of RCC ACHN cells was investigated. The results demonstrated significantly downregulated COP1 expression levels in the RCC intratumors, which was negatively associated with clinicopathological characteristics, such as tumor size, tumor‑node‑metastasis (TNM) stage and lymph node or distant metastasis. COP1 was demonstrated to markedly reduce the colony size of RCC ACHN cells, and inhibit the migration and invasion of ACHN cells. In addition, ETV1 and matrix metalloproteinase 7 (MMP7) mRNA and protein expression levels were significantly downregulated by the overexpressed COP1. Thus, the results of the present study demonstrate the reduced expression of COP1 and the upregulated expression of ETV1 in RCC tissue samples, which was associated with a high tumor-node-metastasis stage of RCC. Furthermore, the overexpression of COP1 in the RCC ACHN cells inhibited the migration and invasion of ACHN cells, and downregulated ETV1 and MMP7 expression levels. The present study demonstrated the tumor suppressive role of COP1 in RCC by inhibiting cell migration.


Extensive subcutaneous emphysema treated with subcutaneous angiocatheters.
Subcutaneous emphysema (SCE) seen in the emergency department is usually the result of traumatic chest injuries, surgical complications, or invasive airway procedures. SCE is usually a self-limiting phenomenon involving the chest wall and neck, though may progress to involve the deeper tissues leading to respiratory and cardiovascular compromise. Emergent intervention is indicated in such cases of extensive SCE, though the ideal approach to its management is not known. We report a case of successful decompression of extensive SCE using subcutaneous placement of angiocatheters.


Paravertebral block as a promising analgesic modality for managing post-thoracotomy pain.
Analgesia following thoracotomy is routinely accomplished using epidural blockage performed by anesthesiologists. More effective pain control can be achieved with continuous paravertebral blockage performed by thoracic surgeons. We aimed to retrospectively analyze the efficacy of paravertebral blockage for managing post-thoracotomy pain. The study included 125 patients who underwent continuous paravertebral blockage for the following types of thoracic surgery: video-assisted thoracoscopic surgery(n = 87), anterior axillary thoracotomy (n = 21), posterolateral thoracotomy (n = 16), and median sternotomy with additional left thoracotomy (n = 1). We retrospectively evaluated the analgesic effects of continuous paravertebral blockage by assessing whether a good cough effort could be performed and whether an additional painkiller was given as a rescue medication. About 115 patients could perform a good cough effort to expectorate sputum immediately after extubation in the operating room. Six patients tolerated postoperative pain well without any oral or rectal non-steroidal anti-inflammatory drugs (NSAIDs). For97 patients postoperative NSAIDs could control thoracotomy pain well. Twenty-two patients were given an additional painkiller stronger than NSAIDs. Three patients complained of nausea postoperatively. Adequate post-thoracotomy pain control was accomplished by continuous paravertebral blockage, with few complications.


Interventions targeting the elderly population to reduce emergency department utilisation: a literature review.
High utilisation of emergency department (ED) among the elderly is of worldwide concern. This study aims to review the effectiveness of interventions targeting the elderly population in reducing ED utilisation. Major biomedical databases were searched for relevant studies. Qualitative approach was applied to derive common themes in the myriad interventions and to critically assess the variations influencing interventions' effectiveness. Quality of studies was appraised using the Effective Public Health Practice Project (EPPHP) tool. 36 studies were included. Nine of 16 community-based interventions reported significant reductions in ED utilisation. Five of 20 hospital-based interventions proved effective while another four demonstrated failure. Seven key elements were identified. Ten of 14 interventions associated with significant reduction on ED use integrated at least three of the seven elements. All four interventions with significant negative results lacked five or more of the seven elements. Some key elements including multidisciplinary team, integrated primary care and social care often existed in effective interventions, while were absent in all significantly ineffective ones. The investigated interventions have mixed effectiveness. Our findings suggest the hospital-based interventions have relatively poorer effects, and should be better connected to the community-based strategies. Interventions seem to achieve the most success with integration of multi-layered elements, especially when incorporating key elements such as a nurse-led multidisciplinary team, integrated social care, and strong linkages to the longer-term primary and community care. Notwithstanding limitations in generalising the findings, this review builds on the growing body of evidence in this particular area.


[Study on the chemical constituents of the active fraction of Polygonum capitatum].
To investigate the chemical constituents of the active fraction of Polygonum capitatum. Various preparative chromatographic techniques were used for the isolation and purification of the compounds in the flavonoid-enriched fraction and their structures were determined by comparison of their physicochemical and chromatographic data with those of the authentic samples and spectral analysis. Fourteen compounds were obtained and identified as 1-O-P-D-(6'-O-galloyl)-glucopyranosyl-3-methoxy-5-hydroxybenzene (1) ,5,7-dihydroxy-4H-chromen-4-one (2), ellagic acid (3), myricetrin (4), hirsutine (5), rutin (6), quercetin-3-O-(2"-O-galloyl)-beta-D-glucopyranoside (7) , quercetin-3-O-( 3"-O-galloyl) -/3-D-glucopyranoside (8), quercitrin (9) , kaempferol-3-O-alpha-L-rhamnopyranoside (10), quercetin-3-O-(2"-O-galloyl) -alpha-L-rhamnopyranoside (11), quercetin-3-O-(3"-O-galloyl) -alpha-L-rhamnopyranoside (12), quercetin (13), kaempferol (14). The flavonoid-enriched fraction contains flavonols and their glycosides as its major components,which might be responsible for the biological effects of Polygonum capitatum. Compounds 1, 8 and 12 are isolated from the genus Polygonum for the first time; Compound 3 is isolated from Polygonum capitatum for the first time.


Frontal fibrosing alopecia in association with Sjögren's syndrome: more than a simple coincidence.
Frontal fibrosing alopecia is a distinctive form of scarring alopecia considered to be a clinical variant of lichen planopilaris. It predominantly occurs in postmenopausal women and has a slowly progressive course. It was first described by Kossard in 1994. Since then the number of reported cases has increased significantly. Coexistence of frontal fibrosing alopecia and autoimmune disorders - such as discoid erythematosus lupus and Sjögren's syndrome - may suggest a common pathogenic background among the diseases.


Identification of the human UDP-glucuronosyltransferases involved in the glucuronidation of combretastatin A-4.
The stilbenic compound (Z)-combretastatin A-4 (CA-4) has been described as a potent tubulin polymerization inhibitor. In vivo, CA-4 binds to tubulin and inhibits microtubule depolymerization, which results in morphological changes in proliferating endothelial cells. Combretastatin A-4 prodrug phosphate is a leading vascular disrupting agent and is currently being evaluated in multiple clinical trials as a treatment for solid tumors. The aim of this study was to identify and characterize the UDP-glucuronosyltransferase (UGT) isoforms involved in CA-4 glucuronidation by incubation with human liver microsomes and a panel of nine liver-expressed recombinant UGT Supersomes (1A1, 1A3, 1A4, 1A6, 1A9, 2B4, 2B7, 2B15, and 2B17). As we observed, the high rate of formation of CA-4 glucuronide (V(max) = 12.78 +/- 0.29 nmol/min/mg protein) and the low K(m) (6.98 +/- 0.65 microM) denoted that UGT1A9 was primarily responsible for the in vitro glucuronidation of CA-4. UGT1A6 was also a significant contributor to CA-4 glucuronidation (V(max) = 3.95 +/- 0.13 nmol/min/mg protein and S(50) = 44.80 +/- 3.54 microM). Furthermore, we demonstrated that the kinetics of CA-4 glucuronidation with liver microsomes but also with a panel of recombinant UGTs is atypical as it fits two different models: the substrate inhibition and also the sigmoidal kinetic model. Finally, experiments conducted to inhibit the glucuronosyltransferase activity in the human liver microsomes assay showed that phenylbutazone, trifluoperazine, propofol, and 1-naphthol effectively inhibited CA-4 glucuronidation.


Videoendoscopic biofeedback: a simple method to improve the efficacy of swallowing rehabilitation of patients after head and neck surgery.
The value of flexible videoendoscopy as a biofeedback tool in conservative swallowing rehabilitation of patients suffering from aspiration after head and neck surgery was examined. For this purpose, the outcomes of conventional swallowing therapy and of swallowing therapy with support of videoendoscopic biofeedback were compared. In the first 40 days of swallowing therapy, videoendoscopic biofeedback significantly increased the chance of therapeutic success, shortening the period of functional rehabilitation in comparison to conventional swallowing therapy. Limitations of this visual biofeedback procedure are poor cognitive skills of the patient, rejection of the procedure by the patient and local factors that make the positioning of the endoscope difficult.


Access to state-of-the-art healthcare: a missing dynamic in consumer selection of a retirement community.
The top ten retirement destinations in the United States are compared to the State of Michigan with regard to the quality of medical care that can be readily obtained in the event of a medical emergency. Access to care during the following three medical emergencies was analyzed: cardiac arrest, thromboembolic (ischemic) stroke, and severe traumatic injury. In all instances, successful treatment is dependent on timely access to care. The authors report that, when combined with the health status of baby boomers and their migratory trends on retirement, access to tertiary medical care for the treatment of cardiac arrest, certified primary stroke centers, and level I trauma centers is the missing dynamic in the choice of retirement community among today's prospective retirees. They recommend that physicians encourage this patient population to consider such factors when choosing a retirement community.


Falling short of the mark: tales of life after hospital discharge.
The purpose of this qualitative study was to explore the everyday issues, challenges, struggles, and needs of elderly, community-dwelling women in the first weeks posthospital discharge. Fourteen elderly women were interviewed in their homes 6 to 8 weeksfollowing hospitalization. In addition, using a process based on photo novella or photovoice, 4 of the women took photographs of their everyday lives. The photos were used as triggers during the interviews. The interviews were analyzed to identify the themes of the women's experiences. The overarching theme was that hospital discharge plans "fall short of the mark" because theyfailed to reflect the complexity of the posthospitalization experience by focusing primarily on very basic physical and medically related needs rather than on the reality of the women's recovery. These findings are alarming given the aging population. The implications for hospital discharge planners, home care service providers, and policy decision makers are discussed.


The etiology of risk: a preliminary model.
The purpose of this paper is to describe an approach that links risk-assessment and theory-directed research. Here we describe a theoretical underpinning to current notions of dynamic risk assessment. The paper has two facets. First, the reframing of a number of concepts such as (i). Stable dynamic factors that we note would be better described as traits and hence have a grounding in the extant general psychological literature on trait theory, (ii). Static risk factors that can be viewed as historical markers of the same underlying psychological dispositions measured by stable dynamic risk factors; (iii). Acute risk factors that are better described as triggering/contextual risk factors (iv). Acute risk factors that should be defined as the state expression of traits triggered by triggering/contextual risk factors. And second, the description of an etiological model of risk- model taking into account the interaction between significant learning events (i.e., developmental variables), psychological vulnerabilities (i.e., marked by static/historical variables and/or stable dynamic risk factors), contextual or triggering factors and their convergence in offense-related acute dynamic risk (i.e., acute psychological states).


Therapeutic Potential of Hyporesponsive CD4(+) T Cells in Autoimmunity.
The interaction between dendritic cells (DCs) and T cells is crucial on immunity or tolerance induction. In an immature or semi-mature state, DCs induce tolerance through T-cell deletion, generation of regulatory T cells, and/or induction of T-cell anergy. Anergy is defined as an unresponsive state that retains T cells in an "off" mode under conditions in which immune activation is undesirable. This mechanism is crucial for the control of T-cell responses against self-antigens, thereby preventing autoimmunity. Tolerogenic DCs (tDCs), generated in vitro from peripheral blood monocytes of healthy donors or patients with autoimmune pathologies, were shown to modulate immune responses by inducing T-cell hyporesponsiveness. Animal models of autoimmune diseases confirmed the impact of T-cell anergy on disease development and progression in vivo. Thus, the induction of T-cell hyporesponsiveness by tDCs has become a promising immunotherapeutic strategy for the treatment of T-cell-mediated autoimmune disorders. Here, we review recent findings in the area and discuss the potential of anergy induction for clinical purposes.


Crossed and uncrossed retinal projections to the hamster circadian system.
The hamster suprachiasmatic nucleus (SCN), site of the circadian clock, has been thought to be equally and completely innervated by each retina. This issue was studied in animals that had received an injection of the tracer cholera toxin subunit B (CTb) conjugated to Alexa 488 into the vitreous of one eye, with CTb-Alexa 594 injected into the other. Retinal projections to the SCN and other nuclei of the circadian system were simultaneously evaluated by using confocal laser microscopy. Each retina provides completely overlapping terminal fields throughout each SCN. Although SCN innervation by the contralateral retina is slightly denser than that from the ipsilateral retina, there are distinct SCN regions where input from one side is predominant, but not exclusive. A dense terminal field from the contralateral retina encompasses, and extends dorsally beyond, the central SCN subnucleus identified by calbindin-immunoreactive neurons. Surrounding the dense terminal field, innervation is largely derived from the ipsilateral retina. The densest terminal field in the intergeniculate leaflet is from the contralateral retina, which completely overlaps the ipsilateral projection. Most nuclei of the pretectum receive innervation largely, but not solely, from the contralateral retina, although the olivary pretectal nucleus has very dense patches of innervation derived exclusively from one retina or the other. Retina-dependent variation in terminal field density within the three closely examined nuclei may indicate areas of specialized function not previously appreciated. This issue is discussed in the context of the melanopsin-containing retinal ganglion cell projections to several nuclei in the circadian visual system.


Quantitative profiling of dual phosphorylation of Fus3 MAP kinase in Saccharomyces cerevisiae.
Mitogen-activated protein kinase (MAPK) signaling is a crucial component of eukaryotic cells; it plays an important role in responses to extracellular stimuli and in the regulation of various cellular activities. The signaling cascade is evolutionarily conserved in the eukaryotic kingdom from yeast to human. In response to a variety of extracellular signals, MAPK activity is known to be regulated via phosphorylation of a conserved TxY motif at the activation loop in which both threonine and tyrosine residues are phosphorylated by the upstream kinase. However, the mechanism by which both residues are phosphorylated continues to remain elusive. In the budding yeast, Saccharomyces cerevisiae, Fus3 MAPK is involved in the mating signaling pathway. In order to elucidate the functional mechanism of MAPK activation, we quantitatively profiled phosphorylation of the TxY motif in Fus3 using mass spectrometry (MS). We used synthetic heavy stable isotope-labeled phosphopeptides and nonphosphopeptides corresponding to the proteolytic TxY motif of Fus3 and accompanying data-dependent tandem MS to quantitatively monitor dynamic changes in the phosphorylation events of MAPK. Phosphospecific immunoblotting and the MS data suggested that the tyrosine residue is dynamically phosphorylated upon stimulation and that this leads to dual phosphorylation. In contrast, the magnitude of threonine phosphorylation did not change significantly. However, the absence of a threonine residue leads to hyperphosphorylation of the tyrosine residue in the unstimulated condition, suggesting that the threonine residue contributes to the control of signaling noise.


Skeletal classification of maxillary and mandibular malpositions.
Criteria used to establish ideal skeletal position of the maxilla and mandible relative to the cranial base is exacting. It must first enhance facial esthetics and facial profile. Secondly, it must improve TMJ health; and finally, it must improve physiologic harmony. Physiologic harmony include alleviation of many medical symptoms such as migraine headaches, neck-shoulder-back pain, myalgia, mouth breathing, otitis media, ringing in the ear, dizziness, vertigo, etc. The Skeletal Archial Analysis is a powerful diagnostic aid. Once the skeletal landmarks are learned, it takes clinicians less than 5 minutes to trace and diagnose. This is because it uses visual references rather than columns of angles and linear measurements. How powerful and accurate is this analysis? If done correctly, patients treated to their anterior arc and correct vertical arc will often times achieve significant facial esthetics, TMJ health, and physiologic harmony. Both the Skeletal Archial Analysis and the Skeletal Classification System indicate whether the disharmony is in the maxilla, mandible, or both. They clearly show in which direction these skeletal structures must be moved to enhance facial appearance and health. In all cases, the direction is to move these structures as close to skeletal Type I, Normal, as physiologically possible. Figure 8 shows a 21-year-old female individual with this skeletal classification. She has ideal maxillary and mandibular A-P position and ideal lower facial height. As can be seen, she has an attractive facial profile and she has no clinical symptoms of temporomandibular disorder or other medical problems. Conversely, patients with facial disharmony often seem to have various medical problems, including premenstrual syndrome and infertility. Once clinicians become adept at using the Skeletal Archial Analysis, they will begin to see many more types of facial disharmonies than previously thought. It then becomes a verbal challenge to accurately describe the multitude of different types of skeletal malpositions. In light of this, it is important that a universal Skeletal Classification System be established to promote better understanding in the diagnosis and treatment of facial-skeletal problems.


Proximal extracranial vertebral artery disease in the New England Medical Center Posterior Circulation Registry.
To describe the clinical features of patients with occlusive disease of the proximal (V1) segment of the vertebral artery. Patients with either occlusion or high-grade stenosis involving the V1 segment were chosen for study from the New England Medical Center Posterior Circulation Registry. The registry is a consecutive series of patients with signs and symptoms of posterior circulation ischemia seen at the New England Medical Center, Boston, Mass, during a 10-year period. Clinical features, radiographic findings, and patient outcome were reviewed. Of the 407 patients in the registry, 80 (20%) had V1 segment lesions. Patients could be classified into 5 groups: (1) V1 disease and coexistent severe intracranial occlusive disease of the posterior circulation (n=22); (2) V1 disease with evidence of artery-to-artery embolism (n=19); (3) suspected V1 disease with artery-to-artery embolism, but with other potential causes of stroke or less certain vascular diagnosis (n=20); (4) V1 disease associated with hemodynamic transient ischemic attacks (n=13); and (5) proximal vertebral arterial dissection (n=6). Hypertension, cigarette smoking, and coronary artery disease were common risk factors. Clinical features, location of infarct, and outcome differed between groups and reflected the presumed mechanisms of stroke. Occlusive disease involving the V1 segment of the vertebral artery is common in patients with posterior circulation ischemia, but is often associated with other potential mechanisms of stroke. However, in a series of patients seen at a tertiary referral center, occlusive disease of the V1 segment was the primary mechanism of ischemia in 9% of patients.


Monocarboxylate Transporters Mediate Fluorescein Uptake in Corneal Epithelial Cells.
To determine the presence of monocarboxylate transporter (MCT) in human and rabbit corneal epithelium and its role in transcellular fluorescein transportation in the cornea. The presence of MCTs in human and rabbit corneal epithelium was determined by RT-PCR and immunohistochemistry. Intracellular fluorescein uptake experiment was performed using cultured human corneal epithelial cells (HCECs). The involvement of MCT in fluorescein uptake was determined by addition of MCT inhibitors to HCECs and acute dry eye model on New Zealand albino rabbits by spectrophotometry, corneal impression cytology, and external eye photographs. MCT-1 and MCT-4 were identified in both human and rabbit corneal epithelia. A longer treatment period and a lower pH value in culture medium increased fluorescein uptake in HCECs. Fluorescein uptake in HCECs was decreased following addition of MCT inhibitors in a concentration-dependent manner. Impression cytology under fluorescent microscopy showed intracellular fluorescein staining in the rabbit cornea with acute dry eye treatment that was decreased following topical treatment of MCT inhibitors. Fluorescein ingress in corneal epithelial cells is mediated by the MCT family. Further study of MCT-mediated transport on HCECs may potentially benefit differential diagnosis and contribute better understandings of ocular surface disorders.


GPC2 Is a Potential Diagnostic, Immunological, and Prognostic Biomarker in Pan-Cancer.
Glypican 2 (GPC2), a member of glypican (GPC) family genes, produces proteoglycan with a glycosylphosphatidylinositol anchor. It has shown its ascending significance in multiple cancers such as neuroblastoma, malignant brain tumor, and small-cell lung cancer. However, no systematic pan-cancer analysis has been conducted to explore its function in diagnosis, prognosis, and immunological prediction. By comprehensive use of datasets from The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), Genotype-Tissue Expression Project (GTEx), cBioPortal, Human Protein Atlas (HPA), UALCAN, StarBase, and Comparative Toxicogenomics Database (CTD), we adopted bioinformatics methods to excavate the potential carcinogenesis of GPC2, including dissecting the correlation between GPC2 and prognosis, gene mutation, immune cell infiltration, and DNA methylation of different tumors, and constructed the competing endogenous RNA (ceRNA) networks of GPC2 as well as explored the interaction of GPC2 with chemicals and genes. The results indicated that GPC2 was highly expressed in most cancers, except in pancreatic adenocarcinoma, which presented at a quite low level. Furthermore, GPC2 showed the early diagnostic value in 16 kinds of tumors and was positively or negatively associated with the prognosis of different tumors. It also verified that GPC2 was a gene associated with most immune-infiltrating cells in pan-cancer, especially in thymoma. Moreover, the correlation with GPC2 expression varied depending on the type of immune-related genes. Additionally, GPC2 gene expression has a correlation with DNA methylation in 20 types of cancers. Through pan-cancer analysis, we discovered and verified that GPC2 might be useful in cancer detection for the first time. The expression level of GPC2 in a variety of tumors is significantly different from that of normal tissues. In addition, the performance of GPC2 in tumorigenesis and tumor immunity also confirms our conjecture. At the same time, it has high specificity and sensitivity in the detection of cancers. Therefore, GPC2 can be used as an auxiliary indicator for early tumor diagnosis and a prognostic marker for many types of tumors.


Aluminum modulates brain amyloidosis through oxidative stress in APP transgenic mice.
Epidemiological studies have implicated aluminum (Al) exposure in the pathogenesis of Alzheimer's disease (AD); however, other studies have failed to confirm these results. Oxidative stress is a feature of AD, and Al can exacerbate oxidative events. This biological property has been suggested as a possible mechanism by which this metal could influence the onset and/or evolution of the disease. To test this hypothesis, we fed transgenic mice that over express human amyloid precursor protein (Tg2576) with a diet enriched in Al and measured isoprostane levels, sensitive and specific markers of in vivo oxidative stress, as well as amyloid b peptide formation and deposition. Here, we show an increase in brain isoprostane levels that correlated with increased amyloid b levels and accelerated plaque deposition in Tg2576 mice but not in wild-type (WT) littermates fed with high dietary Al. Significantly, these in vivo effects of Al were reversed by vitamin E, as judged by a reduction of isoprostane production, amyloid b levels, and plaque deposition. These results indicate that dietary Al can modulate in vivo AD-like amyloidosis in Tg2576 by increasing brain oxidative stress.


General practitioners' assessment of interventions applied to optimize laboratory test utilization: a cross-sectional survey study.
General practitioners (GPs) in the Region of Southern Denmark were randomly allocated to a range of interventions to optimize their use of Vitamin D tests over one year. The aim of the current survey study was to investigate GPs assessment of the interventions. Using REDCap web-platform, we invited 638 GPs to participate in a survey about their experiences of guidelines, feedback reports, non-interruptive alerts, and interruptive alerts. The questions were customized for the different interventions. We received responses from only 131 GPs (21%), but no differences in gender, age, or type of GP clinic were observed between responders and invited GPs. Approximately half of the GPs found that guidelines were helpful, and a similar proportion of GPs read the feedback reports 'often' or 'always'. The pop-up alerts were accepted when used for maximum three months for often-used tests. In contrast, alerts were accepted for long periods for rarely-used tests. The groups that were exposed to the interruptive alert found it 'problematic' that it appeared every time vitamin D was requested. Guidelines and feedback reports on tests numbers were accepted, but it was previously found, that they had little effect on improving the use of biochemical tests. Pop-up alerts in the requesting IT system can produce alert fatigue. Future research should focus on developing feedback reports that - when possible - also include relevant clinical information, and pop-up alerts should for often used tests be displayed only for weeks or a few months, but can be repeated.


Primary Melanoma miRNA Trafficking Induces Lymphangiogenesis.
Melanoma, the deadliest cutaneous tumor, initiates within the epidermis; during progression, cells invade into the dermis and become metastatic through the lymphatic and blood system. Before melanoma cell invasion into the dermis, an increased density of dermal lymphatic vessels is observed, generated by a mechanism which is not fully understood. In this study, we show that, while at the primary epidermal stage (in situ), melanoma cells secrete extracellular vesicles termed melanosomes, which are uptaken by dermal lymphatic cells, leading to transcriptional and phenotypic pro-lymphangiogenic changes. Mechanistically, melanoma-derived melanosomes traffic mature let-7i to lymphatic endothelial cells, which mediate pro-lymphangiogenic phenotypic changes by the induction of type I IFN signaling. Furthermore, transcriptome analysis upon treatment with melanosomes or let-7i reveals the enhancement of IFI6 expression in lymphatic cells. Because melanoma cells metastasize primarily via lymphatic vessels, our data suggest that blocking lymphangiogenesis by repressing either melanosome release or type I IFN signaling will prevent melanoma progression to the deadly metastatic stage.


[Influence of low frequency magnetic field used in magnetotherapy on interleukin 6 (IL-6) contents in rat heart and brain].
The human population is exposed ever more frequently to magnetic fields (MF). This is due to both technological progress and development of the economy as well as to advances made in medical science. That is why the thorough understanding and systematized knowledge about mechanisms by which MF exerts its effects on living organisms play such an important role. In this context the health of MF-exposed people is the subject of particular concern. The aim of the study was to evaluate the effect of extremely low frequency magnetic field (ELFMF) used in magnetotherapy on the concentration of interleukin 6 (IL-6) in rat heart and brain. The male rats were randomly divided into 3 experimental groups: group I - control, without contact with magnetic field; group II - exposed to bipolar, rectangular magnetic field 40 Hz, induction "peak-to-peak" 7 mT 30 min/day for 2 weeks; and group III - exposed to bipolar, rectangular magnetic field 40 Hz, 7 mT 60 min/day for 2 weeks. Concentration of IL-6 in the heart and brain of animals was measured after MF exposure. Exposure to ELFMF: 40 Hz, induction "peak-to-peak" 7 mT 30 min/day for 2 weeks caused a significant IL-6 increase in rat hearts compared to the control group (p < 0.05) and a non-significant IL-6 decrease in rat brain. The magnetic field applied for 60 min resulted in non-significant IL-6 increase in rat hearts compared to the control group and significant IL-6 decrease in rat brain (p < 0.05). The influence of magnetic field on inflammation in the body varies depending on the MF parameters and the affected tissues or cells. Med Pr 2017;68(4):517-523.


Ionic liquids for addressing unmet needs in healthcare.
Advances in the field of ionic liquids have opened new applications beyond their traditional use as solvents into other fields especially healthcare. The broad chemical space, rich with structurally diverse ions, and coupled with the flexibility to form complementary ion pairs enables task-specific optimization at the molecular level to design ionic liquids for envisioned functions. Consequently, ionic liquids now are tailored as innovative solutions to address many problems in medicine. To date, ionic liquids have been designed to promote dissolution of poorly soluble drugs and disrupt physiological barriers to transport drugs to targeted sites. Also, their antimicrobial activity has been demonstrated and could be exploited to prevent and treat infectious diseases. Metal-containing ionic liquids have also been designed and offer unique features due to incorporation of metals. Here, we review application-driven investigations of ionic liquids in medicine with respect to current status and future potential.


Evaluation of a new whole blood cytometric lymphocyte transformation test for immunological screening.
Lymphocyte transformation test (LTT) is usually performed by 3H-thymidine (3H-TdR) incorporation of phytohemagglutinin stimulated lymphocytes. This test presents a lack of standardization as well as a great variability of results making it difficult to compare the results carried out by different laboratories. Flow cytometry (FCM) can precisely evaluate cell kinetics by measuring the DNA content of stained nuclei. We tested a new ready-to-use kit for the blastogenic response of mitogen stimulated lymphocytes in FCM for clinical immunological screening (Blastest, Ylem). Separated peripheral blood lymphocytes from the same donors were also tested with the 3H-TdR method at 72h and results compared to FCM. Our results show a significant correlation between data obtained from FCM and 3H-TdR method. We show that there are no differences in results between different cytometers if CVs are low. Flow cytometry is more precise and reproducible and makes a better standardization feasible, it also offers a simpler and faster way for routine LTT enabling a wider clinical use.


Feasibility, Reproducibility, and Clinical Validity of a Quantitative Chest X-Ray Assessment for COVID-19.
Chest X-ray (CXR) is an essential first-line tool in COVID-19 pneumonia diagnosis and management. Our study aimed at assessing 1) CXR manifestations, frequency, and distribution; 2) the feasibility and repeatability of a CXR severity score; and 3) the correlation between the CXR severity score and clinical and laboratory parameters. We reviewed baseline CXRs and clinical data of consecutive patients who presented to our emergency department and resulted positive at SARS-CoV-2 reverse transcriptase-PCR oropharyngeal swab test from March 1, 2020 to April 6, 2020. Lung abnormalities and their distribution were analyzed. A score of CXR severity was assigned by two radiologists, independently, according to the extent of lung involvement, with a maximum score of 8 for CXR. Correlations between the CXR score and the clinical data were assessed. One hundred fifty-five patients were included; 143/155 (92%) were positive at baseline CXR. Ground-glass opacity was the most common finding (141/143, 99%). Involvement was mainly bilateral (96/143, 67%), with peripheral distribution (79/143, 55%). The mean CXR severity score was 3.3 (±2); interobserver agreement was excellent, with a Cohen's K correlation coefficient of 0.901. The CXR score showed a significant positive correlation with C-reactive protein, lactate dehydrogenase, and fever duration, and a negative correlation with oxygen saturation. Chest X-ray findings are in line with those reported by computed tomography studies. The use of a visual CXR score, easy to assess and highly reproducible, can reflect the clinical severity and help the patients' management.


Standardization of a Protocol for Obtaining Platelet Rich Plasma from blood Donors; a Tool for Tissue Regeneration Procedures.
To develop a protocol for obtaining autologous platelet rich plasma in healthy individuals and to determine the concentration of five major growth factors before platelet activation. This protocol could be integrated into the guidelines of good clinical practice and research in regenerative medicine. Platelet rich plasma was isolated by centrifugation from 38 healthy men and 42 women ranging from 18 to 59 years old. The platelet count and quantification of growth factors were analyzed in eighty samples, stratified for age and gender of the donor. Analyses were performed using parametric the t-test or Pearson's analysis for non-parametric distribution. P < 0.05 was considered statistically significant. Our centrifugation protocol allowed us to concentrate basal platelet counts from 1.6 to 4.9 times (mean = 2.8). There was no correlation between platelet concentration and the level of the following growth factors: VEGF-D (r = 0.009, p = 0.4105), VEGF-A (r = 0.0068, p = 0.953), PDGF subunit AA (p = 0.3618; r = 0.1047), PDGF-BB (p = 0.5936; r = 0.6095). In the same way, there was no correlation between donor gender and growth factor concentrations. Only TGF-β concentration was correlated to platelet concentration (r = 0.3163, p = 0.0175). The procedure used allowed us to make preparations rich in platelets, low in leukocytes and red blood cells, and sterile. Our results showed biological variations in content of growth factors in PRP. The factors influencing these results should be further studied.


Extracavitary primary effusion lymphoma of the anorectum.
We report a case of an extracavitary primary effusion lymphoma occurring in the anorectum of a patient with advanced acquired immune deficiency syndrome. The morphology, null cell immunophenotype, and acquisition of plasma cell markers in this case are typical of the so-called solid variant of primary effusion lymphoma. Lymphoma cells in this case were shown to be co-infected with human herpesvirus-8 and Epstein-Barr virus. Following combination chemotherapy and highly active antiretroviral therapy, this patient has remained in clinical remission for > 3.5 years. The purpose of this report is to add another case to the emerging literature regarding the heterogeneous category of extraserous human herpesvirus-8-associated lymphomas.


Omalizumab is effective in treating severe asthma in patients with severe cardiovascular complications and its effects on sCD200, d-dimer, CXCL8, 25-hydroxyvitamin D and IL-1β levels.
There have been concerns about the cardiovascular safety of omalizumab. In this study, the clinical status of the omalizumab receiving severe asthma patients and the cytokine expressions patterns were investigated. In a pilot study described below we examined the levels of serum eosinophil cationic peptid (ECP), CD200, d-dimer, 25-hydroxyvitamin D (25(OH)D), CXCL8 and IL-1β in asthma patients treated with anti-IgE therapy, to explore their relationship with disease activity, and the impact of anti-IgE therapy impact on those levels. Exercise stress testing and blood samples were taken at all follow up visits from the time of first diagnosis and after 20 months of treatment during the disease remission. Fractional exhaled nitric oxide concentrations and serum levels of sTRAIL, sCD200, D-dimer, ECP, total IgE, IL-1β and Hs-CRP were decreased while CXCL8, 25(OH)D were increased after starting the treatment of anti-IgE. Our first case of a patient, who had both protein C and S deficiency and hence a high risk for thromboembolism, documents for the first time the safety of omalizumab for asthmatic patients with concurrent risk factors contributing to arteriothrombotic events. Omalizumab might be used carefully in patients with cardiovascular diseases.


Tissue distribution of soluble and receptor-bound urokinase in human breast cancer using a panel of monoclonal antibodies.
Current evidence regarding the regulation of urokinase-dependent extracellular proteolysis indicates that plasminogen activation is a surface-associated process. We have compared the histological localization of urokinase plasminogen activator (uPA) and urokinase plasminogen activator receptor (uPAR) in breast cancer sections using a panel of monoclonal antibodies. First, the ability of six different anti-uPA monoclonal antibodies to recognize pro-uPA, uPA, and in vitro-formed complexes of uPA with either soluble uPAR or with plasminogen activator inhibitor type 1 was compared. Then the reactivity of the anti-uPAR antibodies was tested, and the occurrence of an uPA receptor of about M(r) 55,000 in samples from breast carcinoma was assessed by immunoprecipitating the uPA receptor from an in vitro 125I-labeled tumor extract. Immunocytochemical data from adjacent sections of 10 tumor specimens showed that antibodies recognizing free and bound uPA mostly stain the cytoplasm and the membrane of epithelial tumor cells in confined areas of the tumor and some fibroblast-like stromal cells. Acid pretreatment of tumor sections, which removes receptor-bound uPA, causes a strong reduction of the immunocytochemical reactivity of epithelial tumor cells, whereas staining of fibroblast-like cells is not considerably affected. Consistent with these results, epithelial tumor cells were mostly unreactive to anti-uPAR antibodies unless pretreated with acidic buffer, whereas fibroblast-like stromal cells showed a faint but acid-resistant staining with all anti-uPARs. In conclusion, these results show that occupied uPA receptors are definitely present on the membrane of epithelial tumor cells and suggest the occurrence of uPA-uPAR-dependent proteolytic activity on the surface of breast cancer cells.


Ischemic neoangiogenesis enhanced by beta2-adrenergic receptor overexpression: a novel role for the endothelial adrenergic system.
Beta2-adrenergic receptors (beta2ARs) are widely expressed, although their physiological relevance in many tissues is not yet fully understood. In vascular endothelial cells, they regulate NO release and vessel tone. Here we provide novel evidence that beta2ARs can regulate neoangiogenesis in response to chronic ischemia. We used in vivo adenoviral-mediated gene transfer of the human beta2AR to the endothelium of the rat femoral artery and increased beta2AR signaling resulting in ameliorated angiographic blood flow and hindlimb perfusion after chronic ischemia. Histological analysis confirmed that beta2AR overexpression also produced benefits on capillary density. The same maneuver partially rescued impaired angiogenesis in spontaneously hypertensive rats (SHR), whereas gene delivery of the G-protein-coupling defective mutant Ile164 beta2AR failed to provide ameliorations. Stimulation of endogenous and overexpressed beta2AR on endothelial cells in vitro was found to regulate cell number by inducing proliferation and [3H]-thymidine incorporation through means of extracellular receptor-activated kinase and vascular endothelial growth factor. The beta2AR also has novel effects on endothelial cell number through stimulation of proapoptosis and antiapoptosis pathways involving p38 mitogen-activated protein kinase and PI3-kinase/Akt activation. Therefore, beta2ARs play a critical role in endothelial cell proliferation and function including revascularization, suggesting a novel and physiologically relevant role in neoangiogenesis in response to ischemia.


Should the Eigenfactor Replace the Impact Factor?: A Bibliometric Study of Plastic, Reconstructive, and Aesthetic Surgery Journals.
Despite the global acceptance of the impact factor (IF) by researchers and academic institutions as one, criticism has been voiced regarding its effectiveness in evaluating the unbiased impact of a journal. To overcome the limitations and drawbacks of the IF that were presented by the scientific community, they introduced several other citation-based bibliometric indices. All plastic and reconstructive surgery journals were analyzed, and bibliometric indices were extracted from the relevant source. Pearson correlation coefficients were used to determine correlations between the various indices. All correlations in between the various bibliometric indices were found to be positively and statistically significant, ranging from moderately highly associated for the IF and Eigenfactor (r = 0.632) to very strongly associated (r = 0.962) for the IF and the Article Influence Score. In the field of plastic and reconstructive surgery, the Eigenfactor and its derivative, the Article Influence Score, could potentially serve as better indices than the IF in demonstrating the overall picture. This information is based on the inclusion of a greater number of journals in the calculation and subtraction of self-citations, without compromising their correlation with other indices.The use of Eigenfactor and other additional bibliometrics cooperatively with the IF could provide the most extensive evaluation of a journal's scientific impact.


Computed radiography: user-programmable features and capabilities.
Digital or computed radiography (CR) using photostimulable storage phosphor plate technology is becoming increasingly popular in certain clinical applications, such as bedside radiography, where it possesses clear advantages over conventional screen-film imaging. The majority of CR systems in clinical use have been manufactured by Fuji Medical Systems USA, Inc (Stamford, CT) and provide a surprising degree of flexibility. Fuji CR units are delivered with preset menus, hardcopy format, and image-processing parameters for each examination. Of practical importance is that users may change the exam menu and printed film format as well as the image-processing parameters for each examination. There is, however, a lack of documentation describing these features and how they are programmed. This paper addresses these issues. Examples are given on how to change: 1) the printed film format, 2) the contrast and gray-scale processing, 3) spatial frequency enhancement, and 4) the appearance of the operator interface menus.


Identification of nondiabetic heart failure-associated genes by bioinformatics approaches in patients with dilated ischemic cardiomyopathy.
Heart failure (HF) is a common pathological condition affecting 4% of the worldwide population. However, approaches for predicting or treating nondiabetic HF (ND-HF) progression are insufficient. In the current study, the gene expression profile GSE26887 was analyzed, which contained samples from 5 healthy controls, 7 diabetes mellitus-HF patients and 12 ND-HF patients with dilated ischemic cardiomyopathy. The dataset of 5 healthy controls and 12 ND-HF patients was normalized with robust multichip average analysis and the differentially expressed genes (DEGs) were screened by unequal variance t-test and multiple-testing correction. In addition, the protein-protein interaction (PPI) network of the upregulated and downregulated genes was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins database and the Cytoscape software platform. Subsequently, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. A total of 122 upregulated and 133 downregulated genes were detected. The most significantly up- and downregulated genes were EIF1AY and SERPINE1, respectively. In addition, 38 and 77 nodes were obtained in the up- and downregulated PPI network. DEGs that owned the highest connectivity degree were USP9Y and UTY in the upregulated network, and CD44 in the downregulated networks, respectively. NPPA and SERPINE1 were also found to be hub genes in the PPI network. Several GO terms and pathways that were enriched by DEGs were identified, and the most significantly enriched KEGG pathways were drug metabolism and extracellular matrix-receptor interaction. In conclusion, the two DEGs, NPPA and SERPINE1, may be important in the pathogenesis of HF and may be used for the diagnosis and treatment of HF.


SBM recommends policy support to reduce smoking disparities for sexual and gender minorities.
The Society of Behavioral Medicine supports the inclusion of gender and sexual minorities in all local, state, and national tobacco prevention and control activities. These activities include surveillance of tobacco use and cessation activities, targeted outreach and awareness campaigns, increasing access to culturally appropriate tobacco use dependence treatments, and restricting disproportionate marketing to lesbian, gay, bisexual, and transgender communities by the tobacco industry, especially for mentholated tobacco products.


[Preparation and biological safety evaluation of porous n-HA/PA66 composite].
Porous nano-hydroxyapatite/polyamide 66 (n-HA/PA66) composite was developed by injection molding method. Uniformly distributed and interconnected pores with an average size of about 500 microm in matrix were obtained. The evaluation of biological safety of the porous composite including cell cytoxicity test, sensitivity test, pyrogen test, haemolysis test was carried out according to GB/T16886 and GB/T16175. The results showed that the porous n-HA/PA66 composite was of no cytotoxicity, no allergen and pyrogen reactions as well as no hemolytic effect.


Approaches to identify kinase dependencies in cancer signalling networks.
Cells integrate extracellular signals into appropriate responses through a complex network of biochemical reactions driven by the activity of protein and lipid kinases, among other proteins. In order to understand this complexity, new approaches, both experimental and computational, have recently been developed with the aim to identify regulatory kinases and infer their activation status in the context of their signalling network. Here, we review such approaches with particular focus on those based on phosphoproteomics. Integration of kinase activity measurements inferred from phosphoproteomics data with other 'omics' datasets is starting to be used to identify regulatory nodes in biochemical networks. These methodologies may in the future be used to identify patient-specific targets and thus advance personalised cancer medicine.


Risk for early ischemic event after acute myocardial infarction in working males.
We attempt to predict ischemic events in the weeks following the hospital discharge after acute myocardial infarction (AMI) in order to aid occupational physicians in taking return-to-work decisions. Included in the study were 1299 AMI patients from 14 coronary care units in Israel who had been employed before hospitalization and were seen after discharge 1, 2, 4, 6, 9 and 12 months after the first AMI. Cardiovascular accidents included death from cardiovascular disease, recurrent infarction or hospitalization due to congestive heart failure or unstable angina. The rate of a first recurrent cardiovascular accident decreased rapidly over the first few weeks. The risk in the third week was still 51 per 1000 person-months, 13.4 (95% CI: 9.2-19.5) times higher than that after 10 weeks when the incidence reached a low steady state. The major predictors in a logistic regression model for an event were: older age, past history of a cerebrovascular event, and congestive heart failure during the course of hospitalization, but the area under the receiver-operator curve was only 64.4%. We conclude that after acute myocardial infarction, the major risk for a recurrent event is a lapse of time from discharge but not other clinical variables. This should be taken into account when considering a proper timing of return-to-work after an acute myocardial infarction.


The pathophysiology of acne.
Acne is a multifactorial inflammatory disease affecting pilosebaceous follicles. The initial event in the development of an acne lesion is abnormal desquamation of the keratinocytes that line the sebaceous follicle, which creates a microplug or microcomedo. An increase in circulating androgens at the onset of puberty stimulates the production of sebum into the pilosebaceous unit. These events combine to create an environment within the pilosebaceous unit that is favorable for the colonization of the commensal bacteria, Propionibacterium acnes. With proliferation, P acnes secretes various inflammatory molecules and chemotactic factors that initiate and perpetuate the local inflammatory response and possibly induce keratinocyte hyperproliferation as well.


Circ5379-6, a circular form of tumor suppressor PPARα, participates in the inhibition of hepatocellular carcinoma tumorigenesis and metastasis.
This study aimed to investigate the role of circRNAs encoded by PPARα in regulating the pathogenesis processes of hepatocellular carcinoma (HCC). Comprehensive analysis of 3 circular RNA databases revealed multiple circular RNAs within the PPARα gene. The candidate circRNAs were first structurally validated via specific convergent and divergent primer amplification, RNase R treatment, and Sanger sequencing. According to a further validation of the cell viability assay, cell cycle and apoptosis, and transwell assays, the circRNAs correlated to PPARα were obtained. Their functions in tumorigenesis were further validated via the subcutaneous tumor model and the migration model in nude mice. We showed that the overexpression of circ5379-6 decreased cell proliferation, inhibited cell migration and invasion, and induced cell apoptosis in the HCC cell lines. Consistently, in vivo studies in nude mice confirmed that the overexpression of circ5379-6 effectively inhibited the tumorigenesis and metastasis of HCC. We conclude that circ5379-6 plays a role similar to its linear counterpart PPARα to inhibit HCC tumorigenesis and progression.


Reslizumab in the treatment of severe eosinophilic asthma: an update.
A marked heterogeneity is exhibited by asthma both clinically and at the molecular level with different phenotypes driven by diverse mechanistic pathways that require specifically targeted treatments. Biologics aimed at IL-4/13, IL-5 or IgE are proven or potentially effective treatments for patients with difficult to treat eosinophilic asthma. Importantly, it is now widely accepted that biologic-based therapies give significant clinical improvements in those patient populations where asthma phenotypes are taken into account. Such asthma phenotypes have been identified by reproducible and straightforward discriminatory biomarkers. This short review discusses recent studies of the effectiveness of the anti-IL-5 reslizumab in relation to the use of simple reproducible biomarkers in eosinophilic asthma.


Tabrizicola rongguiensis sp. nov., isolated from the sediment of a river in Ronggui, Foshan city, China.
A novel Gram-negative, aerobic, non-spore-forming, non-motile and rod-shaped bacterium, designated J26T, was isolated from the sediment of a river in Ronggui, Foshan city, China. Strain J26T grew optimally at 0 % (w/v) NaCl, pH 6.5-7.5, and 30 °C, and it formed milky white irregular colonies on Reasoner's 2A agar medium. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain J26T had the highest similarity to Tabrizicola aquatica RCRI19T (97.1 %) and formed a distinct clade in the genus Tabrizicola. Cellular components of J26T supported this strain as a member of the genus Tabrizicola. The predominant fatty acids were C18 : 1 ω7c, C18 : 1 ω7c-11 methyl and C16 : 0. Polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphorylethanolamine. Ubiquinone Q-10 was the major respiratory quinone, and the DNA G+C content was 64.2 mol%. However, low 16S rRNA gene sequence similarity and average nucleotide identity (73.56 % for ANIb between strain J26T with RCRI19T) demonstrated that strain J26T should be assigned to a novel species. Moreover, the differences between J26T and RCRI19T in terms of physiological and biochemical properties, such as carbon, nitrogen and sulphur metabolism, further supported that J26T represents a novel species, for which the name Tabrizicola rongguiensis sp. nov. is proposed. The type strain is J26T (=GDMCC 1.2843T=KCTC 92112T).