Phorbol ester-induced disruption of the CD4-Lck complex occurs within a detergent-resistant microdomain of the plasma membrane. Involvement of the translocation of activated protein kinase C isoforms.
Recent studies have highlighted the existence of discrete microdomains at the cell surface that are distinct from caveolae. The function of these microdomains remains unknown. However, recent evidence suggests that they may participate in a subset of transmembrane signaling events. In hematopoietic cells, these low density Triton-insoluble (LDTI) microdomains (also called caveolae-related domains) are dramatically enriched in signaling molecules, such as cell surface receptors (CD4 and CD55), Src family tyrosine kinases (Lyn, Lck, Hck, and Fyn), heterotrimeric G proteins, and gangliosides (GM1 and GM3). Human T lymphocytes have become a well established model system for studying the process of phorbol ester-induced down-regulation of CD4. Here, we present evidence that phorbol 12-myristate 13-acetate (PMA)-induced down-regulation of the cell surface pool of CD4 occurs within the LDTI microdomains of T cells. Localization of CD4 in LDTI microdomains was confirmed by immunoelectron microscopy. PMA-induced disruption of the CD4-Lck complex was rapid (within 5 min), and this disruption occurred within LDTI microdomains. Because PMA is an activator of protein kinase C (PKC), we next evaluated the possible roles of different PKC isoforms in this process. Our results indicate that PMA induced the rapid translocation of cytosolic PKCs to LDTI microdomains. We identified PKCalpha as the major isoform involved in this translocation event. Taken together, our results support the hypothesis that LDTI microdomains represent a functionally important plasma membrane compartment in T cells.


Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) intraindividual variability in older adults: Associations with disease and mortality.
Cognitive intraindividual variability (IIV), or dispersion, has been associated with pathological changes, including cognitive and functional decline. Dispersion is typically assessed with experimental cognitive measures or subtests selected from several batteries, and few studies have examined IIV from a single neuropsychological battery. To address this gap, the current study examined the relationship between the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) IIV, mean cognitive performance, self-reported functioning, and death among 699 individuals between 64 and 94 years of age who were screened for neurological illness and living independently in the community. A coefficient of variation statistic served as the dispersion index and was derived by calculating the within-subject variability of the five RBANS indexes for each participant and dividing this value by the overall test battery mean. Results revealed that increased dispersion and poorer mean performance simultaneously predicted self-reported memory problems. In addition, participants with elevated dispersion at baseline had increased rates of death nine years later, although this lost significance after controlling for comorbid heart disease. Cluster analysis of the higher dispersion scores revealed four distinct profile patterns that did not differ on the outcome variables. Elevated RBANS dispersion is a proxy of co-occurring health problems and may be a useful metric of functional decline and death within community-dwelling geriatric populations.


A quantitative study of the neural changes underlying pyloric stenosis in dogs.
This study aimed to quantify the neural changes in congenital pyloric stenosis in dogs and to study the comparative anatomy between this condition in dogs and that in infantile hypertrophic pyloric stenosis. Eight specimens from the pylorus of dogs with pyloric stenosis and six control specimens were examined using conventional histology and immunohistochemistry for a range of neural antigens. The changes in the proportion of nerves immunoreactive for each antigen were quantified and analysed statistically. The morphology of the nerves in the diseased dogs was similar to that in controls. Only vasoactive intestinal peptide was reduced in expression in dogs (median proportion in control dogs 0.57, in diseased dogs 0.17; P = 0.065). This study demonstrates both morphological similarities and significant differences between closely related conditions in dogs, humans and other species.


[Use of radionuclide isotopes by cardiologists. Results of a French survey. Study group: "Nuclear Cardiology" of the French Society of Cardiology and the Society of Nuclear Medicine and Biophysics].
The authors report the results of an enquiry carried out amongst French cardiologists to determine their opinion about radionuclide investigations in cardiological practice. Of the 5,050 cardiologists contacted, 1,431 (28.3%) replied. The cardiologists were attracted by the non-invasive nature (84%) of radionuclide techniques and their complementarity with other methods of investigation (74%) but regretted their cost (55%), their lick of availability in emergencies (35%) and, in general, their difficult of access (30%). Only 38% of the cardiologists who replied used radionuclide investigation on an everyday basis, this being impossible for some because of the distance to the nearest centre with these facilities (on average 32 km but exceeding 50 km in 29% of cases, and the delay before obtaining an appointment (average 13 days) which was often excessive, especially for myocardial scintigraphy (thallium or equivalent). Each cardiologist prescribed an average of 5 myocardial scintigraphies, 3 pulmonary scintigraphies and 2 radioisotopic ventriculography per month. These results seem to be an overestimation; in fact, radionuclide investigations are relatively underemployed, probably more because of the factors cited above than because of lack interest or quality, these latter two points being generally judged positively by the majority of cardiologists. Cardiologists require more from the conclusions of the investigation than a simple description of the images obtained. As with all other investigations that they perform themselves, the interpretation of the results must take the clinical context into consideration and form part of the diagnostic and therapeutic management of the patient.(ABSTRACT TRUNCATED AT 250 WORDS)


[Effects of arsenic trioxide combined with cisplatin on the growth of human nasopharyngeal carcinoma cells and reversion of RASSF1A hympermethylation].
To investigate the effect of arsenic trioxide (As2O3) combined with cisplatin on expression of RASSF1A in nude mice with human nasopharyngeal carcinoma xenograft. The models of human poorly differentiated nasopharyngeal carcinoma in nude mice were established and randomly divided into four groups, control group (NaCl group), As2O3 group, DDP group and As2O3 + DDP group. The expression of RASSF1A mRNA and protein were detected by Real-time RT-PCR and immunohistochemistry respectively. The methylation rate of RASSF1A promoter CpG islands was analyzed by HRM. Experimental groups could obviously inhibit the growth of tumor and up-regulate the expression of RASSF1A. The methylation rate of RASSF1A in transplanted tumors in experimental groups was lower than the control group. Especially As2O3 combined with DDP were superior to the single drug use. As2O3 inhibits the growth of human nasopharyngeal carcinoma cell strain CNE2 xenograft in nude mice and increases mRNA expression of RASSF1A. As2O3 inhibits the malignant phenotypes of human nasopharyngeal carcinoma cells and reverses hypermethylation of RASSF1A.


Biological and phytochemical investigations of crude extracts of Astragalus creticus.
This study was carried out to isolate the secondary metabolites and to evaluate the antibacterial, antifungal, antioxidant, phytotoxic, anti-leishmanial and α-glucosidase activities of dichloromethane and methanol extracts of whole plant of Astragalus creticus. Preliminary phytochemical screening indicated flavonoids, saponins, tannins and cardiac glycosides in this plant. Phytochemical evaluation of methanol extract resulted in isolation and characterization of Ethyl gallate, 1-triacontanoic acid, quercimeritrin, kaempferol-7-O-β-D-glucopyranose, myricetin, kaempferol, betulinic acid, stigmasterol and Daucosterol. The structures of the compounds were determined by Mass and NMR spectroscopy. The methanol extract exhibited better activity against Staphylococcus aureus (58.75%) while dichloromethane extract was found to be very active against Bacillus subtilis (56.30%).The methanol extract demonstrated highly significant phytotoxic (92.68% at 1000μg/ml) and antioxidant (64.55±0.43%) potential while both extracts identified best inhibition of α-glucosidase enzyme. The plant extracts showed non-significant antifungal and anti-leishmanial activities. To our knowledge, it's a first research study on Astragalus creticus that indicate a great biological and phytochemical potential in it.


Clinical assessment and management of liver fibrosis in non-alcoholic fatty liver disease.
Non-alcoholic fatty liver disease (NAFLD) is among the most frequent etiologies of cirrhosis worldwide, and it is associated with features of metabolic syndrome; the key factor influencing its prognosis is the progression of liver fibrosis. This review aimed to propose a practical and stepwise approach to the evaluation and management of liver fibrosis in patients with NAFLD, analyzing the currently available literature. In the assessment of NAFLD patients, it is important to identify clinical, genetic, and environmental determinants of fibrosis development and its progression. To properly detect fibrosis, it is important to take into account the available methods and their supporting scientific evidence to guide the approach and the sequential selection of the best available biochemical scores, followed by a complementary imaging study (transient elastography, magnetic resonance elastography or acoustic radiation force impulse) and finally a liver biopsy, when needed. To help with the selection of the most appropriate method a Fagan's nomogram analysis is provided in this review, describing the diagnostic yield of each method and their post-test probability of detecting liver fibrosis. Finally, treatment should always include diet and exercise, as well as controlling the components of the metabolic syndrome, +/- vitamin E, considering the presence of sleep apnea, and when available, allocate those patients with advanced fibrosis or high risk of progression into clinical trials. The final end of this approach should be to establish an opportune diagnosis and treatment of liver fibrosis in patients with NAFLD, aiming to decrease/stop its progression and improve their prognosis.


The use of RT-PCR to distinguish between plasmid MnSOD transcripts and endogenous MnSOD mRNA.
We report here a convenient RT-PCR method to distinguish plasmid human MnSOD cDNA transcripts from the endogenous MnSOD gene products without engineering the cDNA insert. When a specific antisense primer for the carrier vector sequence was paired with a sense primer for the human MnSOD cDNA in RT-PCR analysis, a unique amplicon with the expected size was generated in MnSOD cDNA transfected cells but not in the wild type or vector control cells. The same primers were also used in genomic DNA-PCR to demonstrate genomic incorporation of cDNA in stably transfected cells. This method is convenient and specific in determining exogenous cDNA incorporation and expression in transfectants especially when transcripts of cDNA are difficult to separate from the endogenous mRNA by other methods.


The impacts of lens and stereo camera separation on perceived slant in Virtual Reality head-mounted displays.
Stereoscopic AR and VR headsets have displays and lenses that are either fixed or adjustable to match a limited range of user inter-pupillary distances (IPDs). Projective geometry predicts a misperception of depth when either the displays or virtual cameras used to render images are misaligned with the eyes. However, misalignment between the eyes and lenses might also affect binocular convergence, which could further distort perceived depth. This possibility has been largely ignored in previous studies. Here, we evaluated this phenomenon in a VR headset in which the inter-lens and inter-axial camera separations are coupled and adjustable. In a baseline condition, both were matched to observers' IPDs. In two other conditions, the inter-lens and inter-axial camera separations were set to the maximum and minimum allowed by the headset. In each condition, observers were instructed to adjust a fold created by two intersecting, textured surfaces until it appeared to have an angle of 90°. The task was performed at three randomly interleaved viewing distances, monocularly and binocularly. In the monocular condition, observers underestimated the fold angle and there was no effect of viewing distance on their settings. In the binocular conditions, we found that when the lens and camera separation were less than the viewer's IPD, they exhibited compression of perceived slant relative to baseline. The reverse pattern was seen when the lens and camera separation were larger than the viewer's IPD. These results were well explained by a geometric model that considers shifts in convergence due to lens and display misalignment with the eyes, as well as the relative contribution of monocular cues.


Fbxw7β, E3 ubiquitin ligase, negative regulation of primary myoblast differentiation, proliferation and migration.
Satellite cells attached to skeletal muscle fibers play a crucial role in skeletal muscle regeneration. During regeneration, the satellite cells proliferate, migrate to the damaged region, and fuse to each other. Although it is important to determine the cellular mechanisms controlling myoblast behavior, their regulators are not well understood. In this study, we evaluated the roles of Fbxw7 in primary myoblasts and determined its potential as a therapeutic target for muscle disease. We originally found that Fbxw7β, one of the E3 ubiquitin ligase Fbxw7 subtypes, negatively regulates differentiation, proliferation and migration of myoblasts and satellite cells on muscle fiber. However, these phenomena were not observed in myoblasts expressing a dominant-negative, F-box deleted Fbxw7β, mutant. Our results suggest that myoblast differentiation potential and muscle regeneration can be regulated by Fbxw7β.


Optimizing radionuclide sequestration in anion nanotraps with record pertechnetate sorption.
The elimination of specific contaminants from competitors poses a significant challenge. Rather than relying on a single direct interaction, the cooperation of multiple functionalities is an emerging strategy for adsorbents design to achieve the required affinity. Here, we describe that the interaction with the target species can be altered by modifying the local environment of the direct contact site, as demonstrated by manipulating the affinity of pyridinium-based anion nanotraps toward pertechnetate. Systematic control of the substituent effect allows the resulting anion nanotraps to combine multiple features, overcoming the long-term challenge of TcO4- segregation under extreme conditions of super acidity and basicity, strong irradiation field, and high ionic strength. The top material exhibits the highest sorption capacity together with record-high extraction efficiencies after a single treatment from conditions relevant to the used nuclear fuel (Hanford tank wastes, 95%) and legacy nuclear wastes (Savannah River Sites, 80%) among materials reported thus far.


Emerging themes and challenges in understanding youth violence involvement.
Identifies emerging key themes in the articles in this special section regarding child and adolescent involvement in violence. Using a developmental-ecological framework and drawing on consistencies across other studies and reviews, this article is intended to summarize the pertinent findings for clinical child psychology. Current knowledge status, needed further research, clinical implications (preventive and treatment), and relevant policy issues are noted.


Construction of zeolitic imidazolate frameworks-derived NixCo3-xO4/reduced graphene oxides/Ni foam for enhanced energy storage performance.
Direct assembling 2D zeolitic imidazolate frameworks-derived (ZIFs)-derived Ni-Co oxide on Ni foam (NixCo3-xO4/Ni foam) is a very attractive way to obtain high performance for electrochemical energy storage device. In this work, the highly optimized NixCo3-xO4/Ni foam was prepared via facile co-precipitation, ion-exchange method and subsequently composited with rGO, acting as binder-less electrode for high properties hybrid supercapacitors. As electrode materials, the pure Co3O4/Ni foam shows 94.40 C g-1 (209.78 F g-1) at 1 A g-1, while the highly optimized NixCo3-xO4/Ni foam exhibits a high capacity of 870.3 C g-1 (1934F g-1) at 1 A g-1. Compared with NixCo3-xO4/Ni foam, the reduced graphene oxides (rGO) modified NixCo3-xO4/Ni foam electrodes possess a porous conductive structure, displaying more superior capacity of 1440.99 C g-1 (3202.22F g-1) at 1 A g-1 and a higher cycling stability of 76.10% retention value after 1000 cycles. Subsequently, the NixCo3-xO4/rGO/Ni foam electrodes were assembled as a hybrid supercapacitor, exhibiting a maximum energy density of 36.31 Wh kg-1, a maximum power density of 8000 W kg-1 and a good cycling stability of 76.29% retention value after 3000 cycles. The NixCo3-xO4/rGO/Ni foam also could light the blue LED device. Thereby, it is proved that NixCo3-xO4/rGO/Ni foam is a promising materials for hybrid supercapacitors.


Molecular Distillation of Lavender Supercritical Extracts: Physicochemical and Antimicrobial Characterization of Feedstocks and Assessment of Distillates Enriched with Oxygenated Fragrance Components.
Lavandula angustifolia is one of the most widely cultivated non-food crops used in the production of essential oil; it is used in perfumery, aromatherapy, pharmaceutical preparations, and food ingredients. In this study, supercritical fluid extraction (SFE) and molecular distillation (MD) were combined, primarily to enrich scCO2 extracts with lavender oxygenated monoterpenes, avoiding thermal degradation, hydrolysis, and solvent contamination, and maintaining the natural characteristics of the obtained oils. Molecular distillation was developed for the first time for the extraction of crucial lavender fragrance ingredients, i.e., from two scCO2 extracts obtained from dry flower stems of lavender cultivated in Poland and Bulgaria. The best results for high-quality distillates were obtained at 85 °C (EVT) and confirmed that linalyl acetate content increased from 51.54 mg/g (initial Bulgarian lavender extract, L-Bg-E) and 89.53 mg/g (initial Polish lavender extract, L-Pl-E) to 118.41 and 185.42 mg/g, respectively, corresponding to increases of 2.3 and 2.1 times in both distillate streams, respectively. The distillates, light oils, and extracts from lavender were also evaluated for their antimicrobial properties by determining the minimum inhibitory concentration (MIC) by the broth microdilution method. Generally, Gram-positive bacteria and Candida spp. were more sensitive to all distilled fractions and extracts than Escherichia coli (Gram-negative bacteria).


Peptidoglycan-based immunomodulation.
Peptidoglycan (PGN) is a unique component in the cytoderm of prokaryotes which can be recognized by different pathogen-associated molecular patterns (PAMPs) in eukaryotes, followed by a cascade of immune responses via different pathways. This review outlined the basic structure of PGN, its immunologic functions. The immunomodulation pathways mediated by PGN were elaborated. PGN induces specific immunity through stimulating different cytokine release and Th1/Th2-dominated immune responses during humoral/cellular immune response. The nonspecific immunity activation by PGN involves immunomodulation by different pattern recognition receptors (PRRs) including PGN recognition proteins (PGRPs), nucleotide oligomerization domain (NOD)-like receptors (NLRs), Toll-like receptors (TLRs), and C-type lectin receptors (CLRs). The sources and classification of PGRPs were summarized. In view of the stimulating activities of PGN and its monomers, the potential application of PGN as vaccine or adjuvant was prospected. This review provides systematic information on PGN functionalities from the point of immunoregulation, which might be useful in the deep exploitation of PGN.Key points. The immunological functions of PGN were illustrated. Cellular and humoral immunomodulation by PGN were outlined. The use of PGN as vaccine or adjuvant was prospected.


The Chapel Hill hemophilia A dog colony exhibits a factor VIII gene inversion.
In the Chapel Hill colony of factor VIII-deficient dogs, abnormal sequence (ch8, for canine hemophilia 8, GenBank no. ) follows exons 1-22 in the factor VIII transcript in place of exons 23-26. The canine hemophilia 8 locus (ch8) sequence was found in a 140-kb normal dog genomic DNA bacterial artificial chromosome (BAC) clone that was completely outside the factor VIII gene, but not in BAC clones containing the factor VIII gene. The BAC clone that contained ch8 also contained a homologue of F8A (factor 8 associated) sequence, which participates in a common inversion that causes severe hemophilia A in humans. Fluorescence in situ hybridization analysis indicated that exons 1-26 normally proceed sequentially from telomere to centromere at Xq28, and ch8 is telomeric to the factor VIII gene. The appearance of an "upstream" genomic sequence element (ch8) at the end of the aberrant factor VIII transcript suggested that an inversion of genomic DNA replaced factor VIII exons 22-26 with ch8. The F8A sequence appeared also in overlapping normal BAC clones containing factor VIII sequence. We hypothesized that homologous recombination between copies of canine F8A inside and outside the factor VIII gene had occurred, as in human hemophilia A. High-resolution fluorescent in situ hybridization on hemophilia A dog DNA revealed a pattern consistent with this inversion mechanism. We also identified a HindIII restriction fragment length polymorphism of F8A fragments that distinguished hemophilia A, carrier, and normal dogs' DNA. The Chapel Hill hemophilia A dog colony therefore replicates the factor VIII gene inversion commonly seen in humans with severe hemophilia A.


Large-scale comparative metagenomics of Blastocystis, a common member of the human gut microbiome.
The influence of unicellular eukaryotic microorganisms on human gut health and disease is still largely unexplored. Blastocystis spp. commonly colonize the gut, but its clinical significance and ecological role are currently unsettled. We have developed a high-sensitivity bioinformatic pipeline to detect Blastocystis subtypes (STs) from shotgun metagenomics, and applied it to 12 large data sets, comprising 1689 subjects of different geographic origin, disease status and lifestyle. We confirmed and extended previous observations on the high prevalence the microrganism in the population (14.9%), its non-random and ST-specific distribution, and its ability to cause persistent (asymptomatic) colonization. These findings, along with the higher prevalence observed in non-westernized individuals, the lack of positive association with any of the disease considered, and decreased presence in individuals with dysbiosis associated with colorectal cancer and Crohn's disease, strongly suggest that Blastocystis is a component of the healthy gut microbiome. Further, we found an inverse association between body mass index and Blastocystis, and strong co-occurrence with archaeal organisms (Methanobrevibacter smithii) and several bacterial species. The association of specific microbial community structures with Blastocystis was confirmed by the high predictability (up to 0.91 area under the curve) of the microorganism colonization based on the species-level composition of the microbiome. Finally, we reconstructed and functionally profiled 43 new draft Blastocystis genomes and discovered a higher intra subtype variability of ST1 and ST2 compared with ST3 and ST4. Altogether, we provide an in-depth epidemiologic, ecological, and genomic analysis of Blastocystis, and show how metagenomics can be crucial to advance population genomics of human parasites.


Enterococci from Raw-Milk Cheeses: Current Knowledge on Safety, Technological, and Probiotic Concerns.
The present study is focused on the safety, technological characteristics, and probiotic evaluation of Enterococcus species from different artisanal raw milk dairy products, mainly cheeses with ripening. Apart from proteolytic and lipolytic activities, most enterococci show the ability to metabolize citrate and convert it to various aromatic compounds. Long-ripened cheeses therefore have a specific flavor that makes them different from cheeses produced from thermally treated milk with commercial starter cultures. In addition, enterococci are producers of bacteriocins effective against spoilage and pathogenic bacteria, so they can be used as food preservatives. However, the use of enterococci in the dairy industry should be approached with caution. Although originating from food, enterococci strains may carry various virulence factors and antibiotic-resistance genes and can have many adverse effects on human health. Still, despite their controversial status, the use of enterococci in the food industry is not strictly regulated since the existence of these so-called desirable and undesirable traits in enterococci is a strain-dependent characteristic. To be specific, the results of many studies showed that there are some enterococci strains that are safe for use as starter cultures or as probiotics since they do not carry virulence factors and antibiotic-resistance genes. These strains even exhibit strong health-promoting effects such as stimulation of the immune response, anti-inflammatory activity, hypocholesterolemic action, and usefulness in prevention/treatment of some diseases.


Evaluation of novel lipid based formulation of β-Artemether and Lumefantrine in murine malaria model.
The present investigation aims at formulating lipid based drug delivery system of β-Artemether and Lumefantrine and comparative pharmacological evaluation with innovator formulation. Commercial modified oil and indigenous natural fatty acids comprised the oily phase in developing lipidic formulation of β-Artemether and Lumefantrine. The developed system was characterized for mean globule size, stability by freeze thaw cycles, and birefringence. Developed formulation and innovator formulation were compared for their in vivo anti-malarial activity at different dose levels in male Swiss mice, infected with lethal ANKA strain of Plasmodium berghei. The percent parasitemia, activity against time and animal survival period were examined. On fourth day of antimalarial studies, at normal and ½ dose levels, formulations revealed zero percent parasitemia while control showed 33.92±6.00% parasitemia. At 1/10 dose level, developed and innovator formulations revealed zero percent parasitemia upto 11th day, however, three mice from innovator formulation demonstrated recrudescence after 12th day. Both the formulations at normal dose and ½ dose levels showed 100% activity and survival whereas at 1/10 dose level, innovator formulation showed, 62.5% survival. The developed lipidic system of β-Artemether and Lumefantrine exhibited excellent antimalarial activity with 100% survival.


Understanding Cystic Fibrosis Comorbidities and Their Impact on Nutritional Management.
Cystic fibrosis (CF) is a chronic, multisystem disease with multiple comorbidities that can significantly affect nutrition and quality of life. Maintaining nutritional adequacy can be challenging in people with cystic fibrosis and has been directly associated with suboptimal clinical outcomes. Comorbidities of CF can result in significantly decreased nutritional intake and intestinal absorption, as well as increased metabolic demands. It is crucial to utilize a multidisciplinary team with expertise in CF to optimize growth and nutrition, where patients with CF and their loved ones are placed in the center of the care model. Additionally, with the advent of highly effective modulators (HEMs), CF providers have begun to identify previously unrecognized nutritional issues, such as obesity. Here, we will review and summarize commonly encountered comorbidities and their nutritional impact on this unique population.


Tough, Stretchable, Compressive Novel Polymer/Graphene Oxide Nanocomposite Hydrogels with Excellent Self-Healing Performance.
Designing hydrogels with high mechanical properties without sacrificing their self-healing efficiencies remains great challenges. We have fabricated cationic polyacrylamide/graphene oxide (GO) hydrogels by free-radical polymerization of acrylamide (AM) and 2-(dimethylamino)ethylacrylatemethochloride (DAC) in the presence of GO. The mechanical properties and self-healing ability can be tuned by the GO content and the mass ratio of AM and DAC. The ionic bonds between DAC and GO and the hydrogen bonds between AM and GO can efficiently dissipate energy and rebuild the networks. The resulting composite hydrogels possess high stiffness (Young's modulus: ∼1.1 MPa), high toughness (∼9.3 MJ m-3), and high fatigue resistance, as well as high self-healing efficiency (>92% of tensile strength, >99% of tensile strain and >93% of toughness). In addition, the completely dried hydrogels can recover their original mechanical values by spraying water and still possess outstanding self-healing efficiency. Our design can provide better fundamental understanding of physical properties of hydrogels and should enable the development of tough, self-healing hydrogels for practical applications.


[Cardiopulmonary bypass in thoracic surgery].
To analyze advisability of cardiopulmonary bypass in thoracic surgery. We estimated early and long-term results of CPB-assisted thoracic interventions in 31 patients with malignant and benign thoracic diseases and invasion into vital mediastinal structures or with concomitant cardiovascular pathology. Acceptable rates of mortality and morbidity confirm safety of CPB in thoracic surgery while satisfactory long-term outcomes are arguments in favor of this direction of thoracic oncology.


HIV/tuberculosis/hepatitis C virus services for incarcerated populations in Azerbaijan and the Eastern Europe Central Asia region.
The tide of HIV, hepatitis C virus (HCV) and drug-resistant tuberculosis (TB) is a challenge for the penitentiary system in Eastern Europe Central Asia (EECA) region. We have analyzed the existing services for incarcerated individuals with HIV, HCV and TB to assess the current situation in the EECA region. Because of the current criminal-legal system, key risk population with strong linkage to the blood-borne and airborne infections has a high proportion among prisoners. Management of these diseases includes a set of services, such as early detection, counseling, testing and treatment, prevention, harm reduction programme, wide educational and information efforts, and organization of continuity care after release. WHO has developed a set of targets, the only precise achievement of which will reduce the burden of these infections and eliminate them as a public health problem. It is necessary to closely monitor the delivery of HIV, HCV and TB care services in penitentiary system of the EECA countries. The comprehensive operational research will help to develop the most effective practices allowing to achieve the care provision for the entire contingent of the penitentiary system and its continuity in the civil sector. Sustainable and sufficient funding is required as well as enough attention to ensure healthcare services at an appropriate level in the penitentiary system.


Robotics in Simulated COVID-19 Patient Room for Health Care Worker Effector Tasks: Preliminary, Feasibility Experiments.
The coronavirus disease 2019 (COVID-19) pandemic has strained health care systems and personal protective equipment (PPE) supplies globally. We hypothesized that a collaborative robot system could perform health care worker effector tasks inside a simulated intensive care unit (ICU) patient room, which could theoretically reduce both PPE use and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposures. We planned a prospective proof-of-concept feasibility and design pilot study to test 5 discrete medical tasks in a simulated ICU room of a COVID-19 patient using a collaborative robot: push a button on intravenous pole machine when alert occurs for downstream occlusion, adjust ventilator knob, push button on ICU monitor to silence false alerts, increase oxygen flow on wall-mounted flow meter to allow the patient to walk to the bathroom and back (dial-up and dial-down oxygen flow), and push wall-mounted nurse call button. Feasibility was defined as task completion robotically. A training period of 45 minutes to 1 hour was needed to program the system de novo for each task. In less than 30 days, the team completed 5 simple effector task experiments robotically. Selected collaborative robotic effector tasks appear feasible in a simulated ICU room of the COVID-19 patient. Theoretically, this robotic approach could reduce PPE use and staff SARS-CoV-2 exposure. It requires future validation and health care worker learning similar to other ICU device training.


Building a Population Representative Pediatric Biobank: Lessons Learned From the Greater Cincinnati Childhood Cohort.
Background: Biobanks can accelerate research by providing researchers with samples and data. However, hospital-based recruitment as a source for controls may create bias as who comes to the hospital may be different from the broader population. Methods: In an effort to broadly improve the quality of research studies and reduce costs and challenges associated with recruitment and sample collection, a group of diverse researchers at Cincinnati Children's Hospital Medical Center led an institution-supported initiative to create a population representative pediatric "Greater Cincinnati Childhood Cohort (GCC)." Participants completed a detailed survey, underwent a brief physician-led physical exam, and provided blood, urine, and hair samples. DNA underwent high-throughput genotyping. Results: In total, 1,020 children ages 3-18 years living in the 7 county Greater Cincinnati Metropolitan region were recruited. Racial composition of the cohort was 84% non-Hispanic white, 15% non-Hispanic black, and 2% other race or Hispanic. Participants exhibited marked demographic and disease burden differences by race. Overall, the cohort was broadly used resulting in publications, grants and patents; yet, it did not meet the needs of all potential researchers. Conclusions: Learning from both the strengths and weaknesses, we propose leveraging a community-based participatory research framework for future broad use biobanking efforts.


Regulation of the human brain natriuretic peptide gene by GATA-4.
Brain natriuretic peptide (BNP) is a cardiac hormone constitutively expressed in the adult heart. We previously showed that the human BNP (hBNP) proximal promoter region from -127 to -40 confers myocyte-specific expression. The proximal hBNP promoter contains several putative cis elements. Here we tested whether the proximal GATA element plays a role in basal and inducible regulation of the hBNP promoter. The hBNP promoter was coupled to a luciferase reporter gene (1818hBNPLuc) and transferred into neonatal ventricular myocytes (NVM), and luciferase activity was measured as an index of hBNP promoter activity. Mutation of the putative GATA element at -85 of the hBNP promoter [1818(mGATA)hBNPLuc] reduced activity by 97%. To study transactivation of the hBNP promoter, we co-transfected 1818hBNPLuc with the GATA-4 expression vector. GATA-4 activated 1818hBNPLuc, and this effect was eliminated by mutation of the proximal GATA element. Electrophoretic mobility shift assay showed that an oligonucleotide containing the hBNP GATA motif bound to cardiomyocyte nuclear protein, which was competed for by a consensus GATA oligonucleotide but not a mutated hBNP GATA element. The beta-adrenergic agonist isoproterenol and its second messenger cAMP stimulated hBNP promoter activity and binding of nuclear protein to the proximal GATA element. Thus the GATA element in the proximal hBNP promoter is involved in both basal and inducible transcriptional regulation in cardiac myocytes.


Future directions and management of liquid biopsy in non-small cell lung cancer.
Lung cancer represents the world's most common cause of cancer death. In recent years, we moved from a generic therapeutic strategy to a personalized approach, based on the molecular characterization of the tumor. In this view, liquid biopsy is becoming an important tool for assessing the progress or onset of lung disease. Liquid biopsy is a non-invasive procedure able to isolate circulating tumor cells, tumor educated platelets, exosomes and free circulating tumor DNA from body fluids. The characterization of these liquid biomarkers can help to choose the therapeutic strategy for each different case. In this review, the authors will analyze the main aspects of lung cancer and the applications currently in use focusing on the benefits associated with this approach for predicting the prognosis and monitoring the clinical conditions of lung cancer disease.


Improved clinical outcomes of outpatient enhanced recovery hip and knee replacements in comparison to standard inpatient procedures: A study of patients who experienced both.
The benefits of combining enhanced recovery after surgery (ERAS) interventions with an outpatient program for total hip/knee arthroplasty (THA/TKA) are uncertain. This study's main objective was to evaluate adverse events with an ERAS-outpatient compared to standard-inpatient care and secondary objectives were to compare pain, functional recovery, PROMs and satisfaction. The ERAS-outpatient program would result in reduced adverse events compared to standard-inpatient care. An ambidirectional single subject cohort study was conducted on 48 consecutive patients who experienced both a standard-inpatient and an ERAS-outpatient THA/TKA (contralaterally). Adverse event rate according to the Clavien-Dindo scale, the Comprehensive Complications Index (CCI) and the number of unplanned episodes of care were assessed. Postoperative pain on a numeric rating scale, opioid consumption in morphine milligram equivalents, functional recovery, patient reported outcome measures (PROMs) (WOMAC, KOOS, HOOS, Forgotten Joint Score and Patient Joint Perception) and patients' satisfaction were also evaluated. Following the ERAS-outpatient surgery, complication rates were reduced by more than 50% (2.1 vs. 4.4, p<0.001), CCI was significantly lower (12.3 vs. 19.1, p<0.001), and similar unplanned episodes of care were observed (p>0.999). In the first 8 postoperative hours, perceived pain was similar (p>0.805) while opioid consumption was significantly reduced (9.3 vs. 26.5, p<0.001). Patients walked, climbed stairs, showered, performed activities of daily living, practised sports, went back to work sooner (p<0.001), but PROMs were similar between groups at the last follow-up (p>0.188). Patients were more satisfied of the ERAS-outpatient pathway and recommended it significantly more (p<0.002). Compared to the conventional inpatient care, the ERAS-outpatient program proved to be safer, enable faster functional recovery, and improve patients' satisfaction which highlight the importance of following ERAS principles when implementing an outpatient THA/TKA program. III; Ambidirectional Cohort study.


Occurrence of radon in Riyadh groundwater supplies.
A study of 222Rn levels in the ground water supplies of the capital city of Saudi Arabia (Riyadh) was carried out. Such sources contribute up to 34% of the total city water demand. Samples were collected from 90 wells (75 deep and 15 shallow) out of 161 that supply water to six water treatment plants and from three locations within each plant. All samples have low radon levels with an average concentration of 2.99 +/- 0.29 and 3.44 +/- 0.35 Bq L-1 (61.8 +/- 7.8 and 92.9 +/- 9.5 pCi L-1) for the deep and shallow well waters, respectively. Due to water cooling, radon level reduction in the treatment plants was found to be in the range of 74-96%. The plants' product waters were found to have very low levels of radon with an overall average value of 0.49 +/- 0.14 Bq L-1 (13.2 +/- 3.8 pCi L-1).


Relationship between protein folding thermodynamics and the energy landscape.
The origin of protein folding thermodynamics is examined in terms of the energy landscape, employing an off-lattice protein model with scaled non-native attractions, which is continuously tunable between a Go-like model and a highly frustrated system. Extensive statistical temperature molecular dynamics simulations, combined with inherent structure analysis, reveal the intimate connection between the global geometric properties of the energy landscape and the statistical temperature. The basin depth of the energy landscape is shown to play a key role in the first-order-like characteristics of the statistical temperature, which are easily identified by the squared modulus of the potential energy gradient in the microcanonical ensemble.


(18)FDG-PET-scan in staging of primary malignant melanoma of the oesophagus: a case report.
Primary malignant melanoma of the oesophagus is a rare disease, only 262 cases being reported up to June 2005. In general, the prognosis is dismal because of its tendency to present as an advanced neoplasm with aggressive biological behaviour. (18)FDG-PET-scan is a useful tool for evaluation of metastatic disease and locoregional lymph node metastasis. We present herein a case of a young adult with primary malignant melanoma of the oesophagus, followed by a literature review on the subject.


Ovarian metastasis from nongynecologic primary sites: a retrospective analysis of 177 cases and 13-year experience.
Metastasis to the ovary from nongynecologic organs accounts for 9% of all ovarian malignancies. Although the most common nongynecologic primary site of ovarian metastasis is the gastrointestinal tract, metastasis from other sites to the ovary is not uncommon. Differential diagnosis of primary and metastatic ovarian tumors is important; otherwise, appropriate treatment cannot be determined. Furthermore, an optimal treatment strategy for ovarian metastasis from nongynecologic primary sites still needs to be explored. One hundred seventy-seven patients with ovarian metastasis from nongynecologic primary sites admitted to Peking Union Medical College Hospital between May 2005 and May 2018 were retrospectively evaluated. The mean age was 48 years (range, 18-83). Approximately 60% of patients were premenopausal women. The two most common nongynecologic primary sites of ovarian metastasis were the colorectum (68 cases) and stomach (61 cases). In addition to the most common symptoms of abdominal distension (39.0%), abdominal pain (37.9%), and ascites (27.7%), 18.1% of patients presented with abnormal uterine bleeding. Half of the patients who tested serum CA-125 preoperatively had elevated CA-125 levels within the range of 35 U/ml to 200 U/ml. More than 70% of synchronous ovarian metastases were preoperatively misdiagnosed as primary ovarian cancer. Of all included cases, 56.5% achieved optimal cytoreductive surgery (the diameter of the largest residual lesion < 2 cm). The overall 5-year survival rate and median survival time were 10% and 20 months, respectively. The primary site, optimal cytoreductive surgery, tumor differentiation, and postoperative adjuvant treatment were identified as prognostic indicators. The colorectum and stomach are the most common nongynecologic primary sites of ovarian metastasis. Synchronous ovarian metastasis is easily misdiagnosed as primary ovarian cancer. Optimal cytoreductive surgery and postoperative adjuvant treatment can be performed to confer survival benefit in selected patients.


[The role of the clinical laboratory in the evaluation of the tubular function of the kidneys].
Renal tubules contribute to maintenance of the body equilibrium by regulating urinary excretion of electrolytes and low molecular mass components. Many transport mechanisms for regulation of concentrations of various components of the tubular fluid are situated in the renal tubules. Studies on the specification and localization of subcellular mechanisms functioning in the renal tubules is a progressive borderline trend of investigation. A new approach has been used to solve the problems of clinical nephrology and maintenance of the body balance. Processes of calcium, sodium, and monosaccharide reabsorption in the tubular fluid are described in brief.


Role of surgery in patients with primary non-Hodgkin's lymphoma of the stomach: an old problem revisited.
The literature after 1980 dealing with the treatment of primary gastric non-Hodgkin's lymphoma (stages I and II) is reviewed. Gastrectomy is recommended for patients with acute symptoms at presentation or with complications of chemotherapy or radiotherapy. In elective cases, patients with stage I disease may be candidates for gastrectomy as a single therapy, provided that tumour-free resection margins are achieved. There is no evidence of substantial benefit from adding postoperative chemotherapy or radiotherapy after an apparently radical resection. In stage II disease, the best results are achieved with ablative surgery plus adjuvant therapy. The resection volume should be limited to macroscopically involved structures, in principle avoiding total gastrectomy and extensive lymph node dissection, since residual disease may be optimally controlled with radiotherapy or chemotherapy. Primary chemotherapy, with or without radiotherapy, represents an experimental approach; the advantages of sparing the stomach must be balanced against the toxicity of an aggressive chemotherapy regimen and the risk of emergency operation for iatrogenic complications.


Evidence-based supportive care in multiple myeloma.
Multiple myeloma (MM) is a hematological malignancy characterized by an abnormal clone of plasma cells in the bone marrow. MM and its therapy increase the risk of complications like anemia, osteolytic lesions, pain, infections, and renal abnormalities in MM patients. Supportive care for MM patients improves the quality of life. Treatment with bisphosphonates decreases skeletal-related events. Vertebroplasty and kyphoplasty are done in cases of vertebral compression fractures. Prophylactic antibiotics and antivirals can decrease infections related to morbidity. Plasmapheresis in patients with renal dysfunctions decreases dialysis dependency and improve quality of life.


Selegiline (deprenyl) treatment and death of nigral neurons in Parkinson's disease.
We studied the effect of selegiline (deprenyl) treatment on the number of Lewy bodies and neuron counts in the substantia nigra in patients with Parkinson's disease (PD). The number of medial nigral neurons was greater and the number of Lewy bodies fewer in those PD patients who had been treated with selegiline in combination with levodopa as compared with patients who had received levodopa alone. This suggests that selegiline treatment may retard the death of nigral neurons, but alternative explanations, such as the reduction of levodopa dosage in selegiline-treated patients, are possible.


Invited article: The coherent optical laser beam recombination technique (COLBERT) spectrometer: coherent multidimensional spectroscopy made easier.
We have developed an efficient spectrometer capable of performing a wide variety of coherent multidimensional measurements at optical wavelengths. The two major components of the largely automated device are a spatial beam shaper which controls the beam geometry and a spatiotemporal pulse shaper which controls the temporal waveform of the femtosecond pulse in each beam. We describe how to construct, calibrate, and operate the device, and we discuss its limitations. We use the exciton states of a semiconductor nanostructure as a working example. A series of complex multidimensional spectra-displayed in amplitude and real parts-reveals increasingly intricate correlations among the excitons.


A novel hook-shaped enhancement on contrast-enhanced sagittal magnetic resonance image in acute Sheehan's syndrome: a case report.
We report characteristic magnetic resonance (MR) image findings in a case of Sheehan's syndrome. A 37-year-old woman experienced complications of retained placenta and massive bleeding (3600 g) during delivery of a full-term baby. A pituitary function test demonstrated panhypopituitarism. MR image of the pituitary gland on postpartum day 10 revealed swelling of the anterior lobe. A hook-shaped enhancement was demonstrated on a sagittal image. The pituitary stalk, majority of the marginal zone of the anterior lobe, the anterior lobe just in front of the posterior lobe, and posterior lobe were well enhanced. In contrast, the central portion and the superior margin, just in front of the stalk insertion of the anterior lobe, were not enhanced. Anatomically, blood supply to these unenhanced portions of the anterior lobe was via the hypophyseal long portal vein and trabecular artery, which are tributaries of the superior hypophyseal artery that originate far from the internal carotid artery. Based on clinical history and MR image findings, the patient was diagnosed with Sheehan's syndrome and treated with hydrocortisone and levothyroxine. Follow-up MR image revealed marked atrophy of the anterior lobe. The characteristic hook-shaped enhancement in Sheehan's syndrome well reflected the vulnerability to massive bleeding based on the complex pituitary vasculature, which has not been reported previously. MR image with contrast enhancement is useful in the diagnosis of the acute phase of Sheehan's syndrome and in evaluating infarction of the anterior lobe.


Speech perception deficits in poor readers: a reply to Denenberg's critique.
We reply to Denenberg's (1999) recent critique of our work (Mody, Studdert-Kennedy, & Brady, 1997). Denenberg mounted two main lines of criticism, one concerning characteristics of the population sampled for the experimental group, and the other a statistical critique, concerning (a) violation of parametric assumptions for use of the F distribution and (b) our supposed acceptance of the null hypothesis of no differences between experimental and control groups. We show that the first criticism stemmed from a misunderstanding of the experimental hypothesis and that the second can be answered by both parametric and nonparametric comparisons across conditions within the experimental group, without reference to the control group. Thus, our original conclusion stands: The difficulty with rapid /ba/-/da/ discrimination that some children with reading impairment may experience does not stem from difficulty in discriminating the rapid spectral transitions at stop-vowel syllable onsets.


Case of suspected theobromine poisoning in dairy cattle.
High-yielding dairy cows collapsed and died displaying signs of a disturbed central nervous system (muscle tremor, convulsion) and a considerably reduced body condition score. An intense diagnostic screening did not allow to confirm a definite diagnosis. Therefore, further analyses including an evaluation of feeds and feeding were initiated. The herd was fed a total mixed ration (TMR) based on corn and grass silage of moderate nutritive value supplemented with various amounts of chocolate chips. In retrospect, the amount of chocolate chips added to the respective TMR batches could not be quantified. These chips were purchased from a company producing bakery and chocolate products for human consumption and added to the silage and therefore to the TMR in order to increase the energy intake of the animals. Because the TMR, which was fed during the time of the incidence, was no longer available, a sample of a later batch of silage was examined. The amount of chocolate chips was quantified (0.44% per fresh matter), and a theobromine analysis was performed in the chocolate chips of the available batch (69.7 mg/100 g fresh matter). Because of the possible link between chocolate intake and observed signs, an immediate cessation of using the chocolate chips was recommended in addition to an optimisation of the TMR, that is an increase of the energy density. Even though the theobromine intake during the time of the incidence is unknown and information about toxicity of theobromine in ruminants is limited, we suspect that the feeding of chocolate in this case caused all signs including the sudden death of the cows. Further reasons are that no differential diagnoses were established and the problems at the farm stopped after removing the chocolate from the TMR.


Activation of the metabolic sensor-AMP activated protein kinase reverses impairment of angiogenesis in aging myocardial microvascular endothelial cells. Implications for the aging heart.
Impairment of angiogenesis - new capillary blood vessel formation from pre-existing vessels, is frequent in aging tissues and cells. Reduced angiogenesis in aging individuals is associated with increased incidence of myocardial infarctions and other cardiovascular diseases. Therefore there is a need to develop novel strategies to enhance angiogenesis in aging individuals. Our previous study demonstrated aging-related impairment of angiogenesis in aging (vs. young) rat myocardial microvascular endothelial cells (MMEC), and identified reduced activation of the vascular endothelial growth factor (VEGF, the most potent stimulator of angiogenesis) gene as the main underlying mechanism. In the present study we examined the possibility of increasing angiogenesis and activating VEGF gene expression in aging MMECs using a chemical activator of the metabolic sensor - AMP activated protein kinase (AMPK). We hypothesized that activation of VEGF gene in aging MMECs by AMPK would stimulate angiogenesis and reverse the impairment in angiogenesis seen in these cells. We used MMECs isolated from aging (24 months old) Fisher F-344 rats and treated them with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), a specific pharmacological stimulator of AMPK. We examined: 1) in vitro angiogenesis; and 2) the expression of phosphorylated AMPK, VEGF, and P-MAPK/Erk1/2. Treatment of aging MMECs with AICAR increased in vitro angiogenesis and VEGF mRNA expression by 2.1-fold and 3.7-fold, respectively. Furthermore, AICAR treatment resulted in phosphorylation of MAPK/Erk1/2. This study demonstrated the successful use AICAR to reverse aging-related impairment of angiogenesis in aging MMECs by enhancing VEGF gene expression and also identified phosphorylation of MAPK/Erk1/2 as a likely mechanism of these changes.


Immunological characterization of maize starch branching enzymes.
Highly purified fractions of three starch branching enzymes from developing maize (Zea mays L.) endosperm were used to prepare antisera in rabbits. In double diffusion experiments, no immunoprecipitate was observed when branching enzyme IIa or IIb was tested against branching enzyme I antiserum. No immunoprecipitate was formed when branching enzyme I was tested against branching enzyme IIa or IIb antiserum. Increasing amounts of antisera in the above combinations also failed to inhibit enzyme activity. Branching enzyme IIa antiserum cross-reacted and formed spurs with branching enzyme IIb when compared with branching enzyme IIa antigen. Comparison of branching enzyme IIb antiserum with branching enzyme IIa also resulted in an immunoprecipitate. Increasing levels of branching enzyme IIa antiserum inhibited branching enzyme IIb as did the reciprocal combination. The data indicated that branching enzymes IIa and IIb are immunologically similar while branching enzyme I is distinct. The data supports the classification of starch branching enzymes based on genetic, kinetic, and chromatographic properties.


A pooled analysis of interval cancer rates in six European countries.
The objective of this study was to assess detection rates and interval breast cancer (IC) rates from eight programmes in the European Breast Cancer Screening Network. A common data collection protocol was used to explore differences in IC rates among programmes and discuss their potential determinants. Pooled analysis was used to describe IC rates by age, compliance in screening, recall rate, screening detection (SD) rate and expected breast cancer incidence. Participation in screening averaged 77.9% (range 42.6-88.7%), recall rate 5.4% (range 3.3-17.7%) in the initial and 3.4% (range 1.8-8.9%) in the subsequent screening rounds, and SD rate was 60.4 (range 41.6-91) per 10 000 women in initial and 38.5 (range 31.3-62.6) in subsequent screens. IC rate during first 12 months after screening was 5.9 (range 2.1-7.3) per 10 000 women screened negative and 12.6 (range 6.3-15) in the second year of the interval. IC comprised 28% of the IC and SD cancers. The ratio between IC rate and expected incidence was 0.29 for the first 12 months and 0.63 for the 13-24 months period. Sensitivity was higher for the ages 60-69 years and for initial tests than subsequent tests. There were distinct differences in the IC rates between programmes. The results of this study reveal large variations in screening sensitivity and performance. Pooled evaluation of some process indicators within the European breast cancer screening programmes proved to be feasible and is likely to be useful for the future, particularly if it is performed regularly and extensively.


The effect of blinded versus nonblinded interviews in the resident selection process.
To evaluate whether resident applicants' academic performance biases the assessment of nonacademic qualities. In this prospective, descriptive study, 2 blinded (personal statement only) and 1 nonblinded (application) 30-minute interviews were compared for candidates ranking into Top 10, Upper Third, Middle Thirds, Lower Third, and Do Not Rank classes. A total of 234 candidates were interviewed from 2005 to 2007. The association between blinded interviewers for the categories was 87%, 63%, 68%, 73%, and 90% (P = .0000), respectively. Comparing blinded to nonblinded interviewers showed an association of 75% (63%), 71% (86%), 68% (58%), 66% (79%), and 72.7% (82%) (P = .0000), respectively. A strong degree of agreement (Cohen κ, 0.75) for the 2 ranking scores resulted in 90% agreement for Top 10 and Upper Third and 85% for Middle Third and Lower Third categories. No correlation was found between United States Medical Licensing Examination scores and final ranking; moderate agreement was found between ranking and deans' letters (Cohen κ, 0.59, P = .0000). Candidate rankings on nonacademic attributes were not affected by interview type.


Transcriptional regulation of heart valve development and disease.
Aortic valve disease is estimated to affect 2% of the United States population. There is increasing evidence that aortic valve disease has a basis in development, as congenital valve malformations are prevalent in patients undergoing valve replacement surgery. In fact, a number of genetic mutations have been linked to valve malformations and disease. In the initial stages of aortic valve pathogenesis, the valvular interstitial cells become activated, undergo cell proliferation, and participate in extracellular matrix remodeling. Many of these cell properties are shared with mesenchymal progenitor cells of the normally developing valves and bones. Historically, valve calcification was thought to be a passive process reflecting end-stage disease. However, recent evidence describes the increased expression of transcription factors in diseased AoV that are common to valvulogenic and osteogenic processes. These studies lend support to the idea that a developmental gene program is reactivated in aortic valve disease and may contribute to the molecular mechanisms underlying valve calcification in disease.


In vitro transcription of the rat insulin-like growth factor-I gene.
Although the liver is the major source of circulating insulin-like growth factor-I (IGF-I), relatively little is known about the regulation of IGF-I gene transcription in this tissue. Since transcripts are initiated largely in exon 1, we established an in vitro transcription system to evaluate activation of transcription via the major exon 1 initiation site. Transcription of a G-free cassette reporter was directed by rat IGF-I genomic fragments, and the adenovirus major late promoter was used as an internal control. Tissue specificity was demonstrated by a 60-90% decrease in transcripts with spleen extracts as compared with liver. 54 base pairs (bp) of upstream sequence were sufficient to direct IGF-I gene transcription, and activity increased 5-fold with 300 bp of upstream sequence. DNase I footprinting revealed four protected regions between -300 and -60 bp; binding was confirmed by gel shift analysis, and tissue specificity was demonstrated by reduced shifts with spleen extracts. The necessity of transcription factor binding to such sites was established by competition analysis, which revealed a specific decrease in IGF-I transcription in the presence of a competing fragment. Use of this in vitro transcription system should permit analysis of the function of individual transcription factors involved in regulation of IGF-I gene expression.


Release of transforming growth factor beta-1 in a vestibular schwannoma cell line.
Vestibular schwannoma (VS) often displays an irregular growth pattern due to factors which remain unknown. In this study, VS cell lines from tissue removed during surgery were cultured in order to assess the presence of transforming growth factor beta-1 (TGFbeta-1) a multifunctional polypeptide that has different pleiotropic effects on various tissues. The antibody-binding inhibition assay technique was used. The proliferation rate of VS cell lines in vitro was assessed by [3H]thymidine incorporation, with determinations carried out on days 0, 1, 2 and 4 after removal of fetal calf serum (FCS) from the medium. After 48 h of FCS deprivation, cell growth decreased. TGFbeta-1 release also decreased progressively 24 h after removing FCS from the medium, reaching an overall decrease of 50% after 3 days. The cell culturing procedure appeared suitable for VS cells, in that VS cultures were viable for at least 4 months. TGFbeta-1 was initially shown to be released in significant amounts, but also to decrease progressively to values five times lower after 4 days. These data thus support the possibility of a significant association between TGFbeta-1 release and VS cell replication.


Semianalytical thermal analysis of the heat capacity of YAG laser rods.
Based on the theory of semianalytical thermal analysis, we investigate the heat capacity of Nd:YAG laser rods for pumping and cooling. A general expression for the temperature field within Nd:YAG laser rod crystals is obtained for the pumping stage and the relation of the maximum temperature rise with pumping time. We also achieve an expression for the temperature field for the cooling stage and the relation of the maximum temperature rise with cooling time. These results show that, when using the output power of 300 W LD pumped Nd:YAG laser rod crystals for 5 s, the maximum temperature rise in the center of the pump face is 154.79 degrees C. After we stop the pumping for 30 s, the maximum temperature rise drops to 0.8%. These results are in agreement with those reported by others. Our results provide a theoretical basis for the optimized design of a LD end-pumped heat capacity laser.


Informing a Canadian paramedic profile: framing concepts, roles and crosscutting themes.
Paramedicine is a rapidly evolving health profession with increasing responsibilities and contributions to healthcare. This rapid growth has left the profession with unclear professional and clinical boundaries. Existing defining frameworks may no longer align with the practice of paramedicine or expectations of the public. The purpose of this study was to explore the roles paramedics in Canada are to embody and that align with or support the rapid and ongoing evolution of the profession. We used a concurrent mixed methods study design involving a focused discourse analysis (i.e., analysis of language used to describe paramedics and paramedicine) of peer reviewed and grey literature (Phase 1) and in-depth one-on-one semi-structured interviews with key informants in Canadian paramedicine (Phase 2). Data from both methods were analyzed simultaneously throughout and after being merged using inductive thematic analysis. Saturation was reached after 99 national and international grey and peer reviewed publications and 20 in depth interviews with stakeholders representing six provinces, seven different service/agency types, 11 operational roles and seven provider roles. After merging both data sets three framing concepts, six roles and four crosscutting themes emerged that may be significant to both present-day practice and aspirational. Framing concepts, which provide context, include variable contexts or practice, embedded relationships and a health and social continuum. Roles include clinician, health and social advocate, team member, educator, professional and reflective practitioner. Crosscutting themes including patient safety, adaptability, compassion and communication appear to exist in all roles. The paramedic profession is experiencing a shift that appears to deviate or at least place a tension on traditional views or models of practice. Underlying and evolving notions of practice are resulting in intended or actual clinical and professional boundaries that may require the profession to re-think how it is defined and/or shaped. Until these framing concepts, roles and crosscutting themes are fully understood, tested and operationalized, tensions between guiding frameworks and actual or intended practice may persist.


A Systematic Literature Review and Indirect Treatment Comparison of Efficacy of Repository Corticotropin Injection versus Synthetic Adrenocorticotropic Hormone for Infantile Spasms.
Background: Infantile spasms is a rare disease characterized by distinct seizures and hypsarrhythmia. Adrenocorticotropic hormone (ACTH) is available as a natural product (repository corticotropin injection, [RCI]; Acthar® Gel) and as synthetic analogs. RCI is a naturally-sourced complex mixture of purified ACTH analogs and other pituitary peptides approved by the United States Food and Drug Administration as a monotherapy for the treatment of infantile spasms. RCI is commonly used in the United States. Outside the United States, synthetic analogs of ACTH-synthetic ACTH1-24 (tetracosactide) and synthetic ACTH1-39 (corticotropin carboxymethyl-cellulose [CCMC])-are used. The efficacy of RCI may differ from that of synthetic ACTH treatments based on the structure of peptide; however, no head-to-head clinical trials have compared the efficacy of RCI and synthetic ACTH treatments. Objective: A systematic review and indirect treatment comparison of clinical trials was conducted to assess the comparative efficacy of RCI and synthetic ACTH treatments in infantile spasms. Methods: A search was conducted in MEDLINE, EMBASE, and Cochrane databases through September 30, 2020. Relevant clinical trials on RCI or synthetic ACTH therapy and reporting either cessation of spasms or resolution of hypsarrhythmia, separately or as a combined outcome were included. A Bayesian indirect treatment comparison using a fixed-effects model was used for comparative efficacy. Results: Of 473 citations screened, 21 studies were reviewed qualitatively. In the indirect treatment comparison of six eligible clinical trial studies, the odds of achieving efficacy outcomes were five to eight times greater with RCI than with tetracosactide and 14 to 16 times greater than CCMC. This translated to a risk reduction of 10% to 14% and 40% to 50% with RCI versus tetracosactide and CCMC, respectively. For every two to five patients treated, RCI improved efficacy outcomes in one additional patient compared to synthetic ACTH (adjusted number needed-to-treat). Conclusions: Based on the available limited evidence, results suggest RCI may be more efficacious for infantile spasms than synthetic ACTH treatments. Our findings provide a blueprint to inform the design of future prospective studies for the treatment of infantile spasms.


Phenolic Metabolites in Plasma and Thigh Meat of Chickens Supplemented with Grape Byproducts.
Grape byproducts are rich sources of polyphenols with powerful antioxidant and health-promoting effects. The impact of supplementing chicken diets with grape byproducts on plasma and thigh meat concentrations of phenolic metabolites was evaluated by analyzing samples by high-performance liquid chromatography quadrupole time of flight mass spectrometry. Chickens were fed three experimental diets: Control diet, Control+8% grape pomace, and Control+0.1% grape seed extract. In plasma, 32 phenolic metabolites were identified, some of which were conjugated catechin/epicatechin metabolites exclusively identified in chickens fed diets enriched in grape byproducts. Also, these chickens showed significantly higher plasmatic concentrations of 21 phenolic metabolites. In thigh meat, 14 phenolic metabolites were identified, but no differences were found between diets. Higher plasmatic tocopherol was found when supplementing diets with grape byproducts, while no changes were observed in meat. Thus, supplementing chicken diets with grape byproducts leads to a significant increase in the circulation of phenolic metabolites and tocopherol.


Calcium-selective ion channel, CaT1, is apically localized in gastrointestinal tract epithelia and is aberrantly expressed in human malignancies.
CaT1 is a highly selective calcium entry channel that has been proposed to be responsible for apical calcium entry in the vitamin D-regulated transcellular pathway of Ca(2+) absorption; however, the lack of a CaT1 antibody suitable for immunohistochemistry has prevented the direct testing of this hypothesis by the localization of CaT1 protein in the gastrointestinal tract and other tissues. In this study, we developed two CaT1 antibodies and have used them to establish for the first time that CaT1 localizes to the apical membrane of intestinal absorptive cells, thereby providing the first direct evidence that this protein is in fact an apical entry channel in the gastrointestinal tract. In addition, we found that CaT1 protein is highly expressed in a number of exocrine organs including pancreas, prostate, and mammary gland, suggesting an, as yet, unrecognized role in secretory epithelia. Finally, we found CaT1 protein to be present at elevated levels in comparison with normal tissues in a series of prostate, breast, thyroid, colon, and ovarian carcinomas, consistent with previous reports of up-regulation of CaT1 mRNA in prostate cancer tissues. Our findings indicate that CaT1 is likely to serve as a component of transcellular calcium transport mechanisms in many tissues and epithelial cancers.


Variable selection in monotone single-index models via the adaptive LASSO.
We consider the problem of variable selection for monotone single-index models. A single-index model assumes that the expectation of the outcome is an unknown function of a linear combination of covariates. Assuming monotonicity of the unknown function is often reasonable and allows for more straightforward inference. We present an adaptive LASSO penalized least squares approach to estimating the index parameter and the unknown function in these models for continuous outcome. Monotone function estimates are achieved using the pooled adjacent violators algorithm, followed by kernel regression. In the iterative estimation process, a linear approximation to the unknown function is used, therefore reducing the situation to that of linear regression and allowing for the use of standard LASSO algorithms, such as coordinate descent. Results of a simulation study indicate that the proposed methods perform well under a variety of circumstances and that an assumption of monotonicity, when appropriate, noticeably improves performance. The proposed methods are applied to data from a randomized clinical trial for the treatment of a critical illness in the intensive care unit.


A Multicenter Study Evaluating Ceftriaxone and Benzathine Penicillin G as Treatment Agents for Early Syphilis in Jiangsu, China.
The aim of this study was to assess the efficacy of ceftriaxone and benzathine penicillin G (BPG) in nonpregnant, immunocompetent adults with early syphilis because there is a lack of clinical evidence supporting ceftriaxone as an alternative treatment for early syphilis without an human immunodeficiency virus coinfection. A randomized, open-label controlled study evaluating the efficacy of ceftriaxone and BPG was conducted in 4 hospitals in Jiangsu Province. Treatment comprised either ceftriaxone (1.0 g, given intravenously, once daily for 10 days) or BPG (2.4 million units, given intramuscularly, once weekly for 2 weeks). A serological response was defined as a ≥4-fold decline in the rapid plasma reagin (RPR) titer. In all, 301 patients with early syphilis were enrolled in this study; 230 subjects completed the follow-ups. The serological response at 6 months of follow up was observed in 90.2% in ceftriaxone group and 78.0% in BPG group (P = .01). There was no significant difference between treatment groups in patients with primary or early latent syphilis, but among patients with secondary syphilis the difference was highly significant (95.8% vs 76.2%; P < .01). Moreover, patients exhibiting a Jarisch-Herxheimer reaction after treatment might have a shorter period before a serological response (P = .03). In this study, ceftriaxone regimen was noninferior to the BPG regimen in nonpregnant, immunocompetent patients with early syphilis. ChiCTR-TQR-13003624.


[Intermolecular interactions between fluorescent probes bound to linear DNA].
Intermolecular interactions of fluorescent probes bound to linear DNA. Several fluorescent probes can be widely used in determining the base content, the geometry and the possible conformational transitions of linear and circular DNAs in solution. Data are presented showing that Tb3+ and DAPI bind independently to DNA and can therefore be used to monitor the G+C and A+T content of the nucleic acid respectively.


A new species of Leptodactylus Fitzinger (Anura, Leptodactylidae, Leptodactylinae) from montane rock fields of the Chapada Diamantina, northeastern Brazil.
In this paper, we describe a new species of the Leptodactylusfuscus group on the basis of adult morphology and advertisement call, occurring restricted to montane rock fields of the Chapada Diamantina, northern portion of the Espinhaço Range, central State of Bahia, northeastern Brazil. In addition, we re-describe the advertisement call ofL. camaquara from its type locality. Leptodactylus oreomantis sp. nov. represents the first species of the genus occurring restricted to montane rock fields of the Chapada Diamantina, northeastern Brazil, whereas the other three species of the L. fuscus group assumed to be restricted to montane field environments (L. camaquara, L. cunicularius, and L. tapiti) occur in association with mountain ranges of southeastern or central Brazil.


Technical Potential of Biogas Technology to Substitute Traditional Fuel Sources and Chemical Fertilizers and Mitigate Greenhouse Gas Emissions: The Case of Arba-Minch Area, South Ethiopia.
A study was conducted in South Ethiopia with the aim of assessing the technical potential of biogas energy in replacing traditional bioenergy and chemical fertilizers and mitigating greenhouse gas emissions. A household survey with both a quantitative and qualitative approach was employed for data collection. Primary data were gathered from 182 biogas adopters as well as 10 key informants and three group discussions. Secondary data were also collected from different sources. The average biogas production potential of installed biogas plants was 205 m3 per day. The average reduction in use of firewood, charcoal, dung cakes, and crop residues due to biogas adoption was 66%, 72%, 68%, and 89%, respectively. The use of bio-slurry as an organic fertilizer reduced the quantity of chemical fertilizers used by more than 50% per household per year. The reduction in the quantity of biofuel consumption reduced the volume of greenhouse gas emissions by 418 tons of carbon dioxide equivalents per household per year. If the reduced firewood and charcoal use reduced the felling of live trees, this could potentially conserve 45 ha of forest per household per year. Therefore, biogas energy could help reduce the anthropogenic pressure on forest resources by addressing the major drivers of deforestation and forest degradation.


The relevance of social network concepts to sexually transmitted disease control.
Many of the concepts of social network analysis have been tacit assumptions of sexually transmitted disease control efforts for decades. With the advent of AIDS in the 1980s, an overt rapprochement between these two fields--previously separated by culture, context, and language--was made. Social network constructs have immediate appeal to disease control workers, who view many diseases as following the conduits of social interactions. STDs and HIV, in turn, provide network analysts and those who model disease transmission with substantial sets of empirical data that test and illuminate theory. Disease control efforts can be enhanced by incorporating network concepts overtly into current practices. Such concepts offer a path to better delineation of groups at risk, to a better understanding of the interaction of personal risk taking and the social context, and to evaluation of control mechanisms.


Aging of masticatory efficiency in healthy subjects: electromyographic analysis--Part 2.
The masticatory process identifies the level of the individual's masticatory ability and provides important information for an adequate diagnosis of the masticatory function. The purpose of this cross-sectional study was to evaluate the influence of age on habitual and non-habitual mastication by means of the values of the ensemble average of masticatory cycles. All volunteers were Brazilian, Caucasian, fully dentate (except for Group I--mixed dentition), aged 7-80 years and divided into five groups: I (7-12 years), II (13-20 years), III (21- 40 years), IV (41-60 years) and V (61-80 years). Except for Group V, which comprised nine women and eight men, all groups were equally divided with respect to gender (20 M/20 F). All subjects were nasal breathers, had normal occlusion and no parafunctional habits or symptoms of temporomandibular dysfunction (RDC/TMD). The masticatory process was analyzed during habitual mastication of peanuts and raisins, and non-habitual mastication of ParafilmM, for 10 seconds each. The resulting electromyographic data were evaluated using SPSS 19.0 software for Windows. ANOVA (analysis of variance) followed by the Duncan test were used to compare the efficiency of the masticatory cycle between age groups. Multivariate analysis (General Linear Models) was used to analyze the effect of age groups and gender on the efficiency of themasticatory cycle, to compare groups (p < 0.05). The results showed that age is directly associated with the changes in masticatory process in healthy subjects.


[Chemotherapy targeting regional lymph nodes by gastric submucosal injection of liposomal adriamycin in patients with gastric cancer].
We investigated the delivery of adriamycin (ADR) to the regional lymph nodes of the stomach following the gastric submucosal injection of liposomal adriamycin (Lipo-ADR) in 34 gastric carcinoma patients, as well as following intravenous administration of free ADR (F-ADR) in 18 patients, then followed these patients for a minimum of 5 years or until death. Prior to radical gastrectomy. Lipo-ADR was endoscopically injected into the gastric submucosa adjacent to the primary tumor via a needle-tipped catheter. After Lipo-ADR injection, the ADR concentration in the primary and secondary drainage lymph nodes was higher than in the other regional lymph nodes. Thus, the regional nodes more susceptible to the involvement of metastasis showed higher levels of ADR. In contrast, the intravenous administration of F-ADR produced a similar and far lower ADR concentration in all the nodes. Delivery of ADR to the primary drainage lymph nodes following injection of 5 mg of Lipo-ADR (n = 19) was compared with delivery to the left gastric artery lymph nodes after intravenous administration of an equal dose of Lipo-ADR. The ADR levels (microgram/g) after gastric submucosal injection were 15.1 +/- 8.30 on day 1 (n = 4) and 11.9 +/- 4.80 on day 4 (n = 6), whereas, the ADR levels after intravenous administration were 0.29 +/- 0.10 on day 1 (n = 4) and 0.36 +/- 0.0 on day 4 (n = 2). The differences between the two groups were significant (p < 0.05). The ADR levels after the gastric submucosal injection were far higher than those after intravenous administration. These findings indicate that the gastric submucosal injection of Lipo-ADR can specifically deliver ADR to the regional lymph nodes at high concentrations. Disease-free survival of the stage III a-b patients (n = 7) with this regional lymph nodes-targeted chemotherapy was 71.4% in 5 years, while that with intravenous F-ADR administration (n = 5) was 60.0%. This preoperative adjuvant chemotherapy targeting the regional lymph nodes may be effective in preventing the recurrence of gastric carcinoma.


Identification of pyroglutamyl peptides in Japanese rice wine (sake): presence of hepatoprotective pyroGlu-Leu.
Japanese rice wine, sake, is made from steamed rice, water, and lactic acid by "multiple parallel fermentation" with mold (Aspergillus oryzae) and yeast (Saccharomyces cerevisiae). Nineteen pyroglutamyl peptides were identified in commercially available sake. Among them, pyroGlu-Leu and pyroGlu-Gln were the major constituents. PyroGlu-Leu has been demonstrated to attenuate hepatitis and colitis in animal models. Commercial products (n = 5) contained pyroGlu-Leu at concentrations ranging from 40 to 60 μM (10-15 mg/L). The pyroGlu-Leu content in sake mash increased during the fermentation processes. However, no pyroGlu-Leu was produced by yeast inoculated into preheated mash. Furthermore, addition of (13)C-Leu to the mash did not increase the ratio of pyroGlu-(13)C-Leu to pyroGlu-(12)C-Leu. On the other hand, digestion of steamed rice with A. oryzae proteases increased the pyroGlu-Leu content. These results indicate that pyroGlu-Leu in sake is produced from rice proteins by digestion with A. oryzae proteases.


DNA barcoding identification of Greek freshwater fishes.
Biodiversity is a key factor for the functioning and efficiency of an ecosystem. Greece, though covering a relatively small surface area, hosts a great deal of species diversity. This is especially true for freshwater fishes. In recent years, the traditional methods of species identification have been supplemented by the use of molecular markers. The present study therefore aims to extensively produce DNA barcodes for Greek freshwater fish species and investigate thoroughly if the presently accepted species classification is in agreement with molecular data. A 624-bases long fragment of the COI gene was sequenced, from 406 freshwater fish specimens belonging to 24 genera and originating from 18 lake and river sites. These sequences were used along with 596 sequences from the same genera, recovered from BOLD, for the construction of phylogenetic trees and the estimation of genetic distances between individuals. In total, 1002 sequences belonging to 72 species were analyzed. The method was found to be effective for 55 of 72 studied species. 17 closely related species with low interspecific genetic distances were observed, for which further study is proposed. It should also be noted that, in four cases, cryptic diversity was observed, where groups originally identified as one species exhibited genetic distance great enough to be separated into discrete species. Region specific haplotypes were also detected within populations of 14 species, giving the possibility to identify even the geographic origin of a species. Our findings are discussed in the light of the rich history of the Balkan peninsula and provide a significant steppingstone for the further study of Greek and European freshwater fish biodiversity.


Inhibition of systemic inflammatory response with sodium nitroprusside in open heart surgery.
A nitric oxide donor, sodium nitroprusside has been reported to reduce the inflammatory response during cardiopulmonary bypass (CPB). To investigate this, a double-blind and prospective study was conducted. Twenty patients with multi vessel coronary disease were randomly chosen to form study (SNP) and control groups. In the SNP group, 0.5 microg/kg/min sodium nitroprusside were administered for 20 min right after the release of the aortic crossclamp. Mac-1 (CD11b/CD18) leukocyte adhesion molecule expressions, interleukin-6 levels were measured from radial artery blood as well as leukocyte and platelet counts in both groups at 6 different time points: a) before anesthesia, b) after heparin administration, c) after aortic crossclamp release, d) after protamine administration, e) 3 hours after the termination of CPB, f) 24 hours after the termination of CPB. The increase in Mac-1 expressions were not different between the two groups at any time point except the measurements after the administration of protamine. At this time point, Mac-1 expressions were not different between the groups (99.8+/-30.7 vs 134.6+/-95.1%, p=0.076), but higher when compared with the preinduction levels. IL-6 levels for SNP and control groups was 89+/-43 and 215+/-131 pg/dL, respectively (p=0.016) 3 hours after the termination of CPB. Twenty-four hours after the termination of CPB, IL-6 levels were still significantly higher in the control group (47+/-27 vs 111+/-68 pg/dL, p=0.039). Leukocyte and platelet counts were not different at any time point between the groups. Systemic inflammatory response in patients undergoing CPB can be reduced to a certain level with sodium nitroprusside, especially the activation of vascular endothelial cells can be inhibited, but activation of leukocytes still takes place.


[Gastrojejunostomy for irresectable gastric cancer with pyloric stenosis-new role of surgery in the era of S-1].
We report a patient with an advanced gastric cancer complicated by pyloric stenosis who was effectively treated by S-1 mono-therapy after gastrojejunostomy. A 62-year-old man consulted a general practitioner for abdominal pain and anorexia. Gastric roentgenography and upper gastrointestinal endoscopy showed gastric cancer(Borrmann Type 3) with pyloric stenosis. He was referred to our department. He underwent laparotomy, which revealed a T4 tumor invading the pancreas head, but neither liver nor peritoneal metastasis. A gastrojejunostomy was made. After the operation, chemotherapy of S-1(120 mg/day, day 1-21)+cisplatin(100 mg/day, day 8)was administered. After 2 courses, level of tumor marker decreased remarkably and abdominal enhanced computed tomography showed a significant size reduction of lymph nodes and that direct invasion to the pancreas was not clear any more. Second laparotomy was carried out and curative surgery was performed. After 4 courses of S-1(120 mg/day, day 1 approximately 28)mono-therapy as adjuvant chemotherapy, bone metastasis was confirmed by scintigram. Then methotrexate+5-FU, irinotecan+cisplatin and cisplatin+paclitaxel were chosen as second-, third-and fourth-line chemotherapy, which were not effective for long. He died 572 a days after the initial surgery. In the past, gastrojejunostomy was regarded as useful palliative treatment for those with gastric outlet stenosis to ameliorate the QOL. As S-1 is taking major role in the chemotherapy for advanced gastric cancer recently, usefulness of bypass surgery for such patients is highlighted even for longer survival time.


Increased expression of epidermal growth factor receptor during gastric ulcer healing in rats.
Expression of epidermal growth factor receptor (EGFR) was studied immunohistochemically in rat gastric mucosa during healing of acetic acid-induced ulcers. In normal control gastric oxyntic mucosa, EGFR was expressed in proliferative zone cells and in some parietal cells. In mucosa of the ulcer margin, at 3, 7, and 16 days after ulcer induction, there was a 75-fold increase (over controls) in the number of cells expressing EGFR. Seventy percent of ulcers healed by the 16th day, and all were healed by the 25th day. The mucosal scar that replaced the ulcer was composed of dilated glands lined with poorly or aberrantly differentiated cells showing persistence of increased EGFR expression. An increased EGFR expression indicates an important role of EGF in ulcer healing and scar formation.


Right ventricular failure: a comorbidity or a clinical emergency?
There has been ample data providing a convincing perception about the underlying mechanism pertaining to left ventricle (LV) hypertrophy progressing towards LV failure. In comparison, data available on the feedback of right ventricle (RV) due to volume or pressure overload is minimal. Advanced imaging techniques have aided the study of physiology, anatomy, and diseased state of RV. However, the treatment scenario of right ventricular failure (RVF) demands more attention. It is a critical clinical risk in patients with carcinoid syndrome, pulmonary hypertension, atrial septal defect, and several other concomitant diseases. Although the remodeling responses of both ventricles on an increase of end-diastolic pressure are mostly identical, the stressed RV becomes more prone to oxidative stress activating the apoptotic mechanism with diminished angiogenesis. This instigates the advancement of RV towards failure in contrast to LV. Empirical heart failure (HF) therapies have been ineffective in improving the mortality rate and cardiac function in patients, which prompted a difference between the underlying pathophysiology of RVF and LV failure. Treatment strategies should be devised, taking into consideration the anatomical and physiological characteristics of RV. This review would emphasize on the pathophysiology of the RVF and the differences between two ventricles in molecular response to stress. A proper insight into the underlying pathophysiology is required to develop optimized therapeutic management in RV-specific HF.


[The mechanism of anti-insulin effect of apoprotein B].
The existence of common epitope in insulin molecule and apolipoprotein B one was shown by means of enzyme immunoassay. Similar epitopes were revealed in apoB-containing lipoproteins (VLDL and LDL) by dot-immunobinding and immunoelectroblotting. Epitopes locate on the surface of lipoproteins and are not screened by lipids. The existence of common epitopes is the reason of competition between insulin and LDL. The experiments with isolated perfused rat hindquarter demonstrate that insulin increased the glucose uptake by muscle and LDL decreased it. Simultaneous perfusion with LDL and insulin leads to reduced insulin action due to completion for insulin receptors. After the recovery of S-S bounds apoB forms some proteins, containing common epitopes with insulin. The presence of such proteins was shown in lipoprotein-free serum. Apoprotein B and its derivates seem to be insulin antagonists with marked antiinsulin action.


Assessing the Potential Impact of Land Use on Carbon Storage Driven by Economic Growth: A Case Study in Yangtze River Delta Urban Agglomeration.
Economic development and land-use change can strongly affect terrestrial ecosystems' carbon balance. This paper quantifies the changes in land use of Yangtze River Delta urban agglomeration (YRD) in 2020 and 2035 under three economic growth scenarios, exploring the concurrent impact on carbon storage. The results showed that the land carbon storage of YRD had decreased by 1453.80 Tg in 2000-2020, and will continue to decrease by 982.38 Tg, 1417.62 Tg, and 1636.21 Tg under the scenarios of a slow, medium, and rapid economic growth from 2020 to 2035, respectively. The large-scale occupation of cultivated land and woodland for construction land caused by economic development and population growth was an important reason. The occupation of cultivated land by construction land in Nanjing, Shanghai, and its surrounding areas had further intensified, while the reduction in carbon storage caused by the reduction in woodland had become more prominent in Hangzhou, Shaoxing, Jinhua, and the surrounding areas.


[A tribute to prominent African American dentists].
If today, American society has undeniably changed, this has been made possible by the selflessness, courage and perseverance of previous generations. Among them are the black American dentists, who met constant opposition. This paper pays homage to their memory.


Insulin-like growth factor (IGF) binding to cell monolayers is directly modulated by the addition of IGF-binding proteins.
Insulin-like growth factor-I (IGF-I) binds to specific receptors and IGF-binding proteins (IGFBPs) that are present on cell surfaces. The analysis of [125I]IGF-I binding to human fibroblasts is complicated by IGFBPs on the cell surface and their release into the medium during the binding assay. This release alters the distribution of [125I]IGF-I between type I IGF receptors and both soluble as well as cell surface-associated IGFBPs. In the present study we have determined the effects of three different forms of IGFBPs on [125I]IGF-I binding to cell surface binding sites of human fetal fibroblasts (GM10 cells) and porcine smooth muscle cells. Human 29,000 mol wt (Mr; IGFBP-1), bovine 34,000 Mr (IGFBP-2), and bovine 46,000 Mr (IGFBP-3) forms of IGFBP were compared. Each of the three IGFBPs inhibited [125I]IGF-I binding to the cell surface of both cell types. This effect was due to increased binding of [125I]IGF-I by the IGFBPs in the assay buffer. At equimolar concentrations, IGFBP-3 was more effective than either IGFBP-1 or IGFBP-2 in blocking cell surface binding. The addition of increasing concentrations of unlabeled IGF-I in the presence of each IGFBP showed that either IGFBP-1 or IGFBP-3, but not IGFBP-2, resulted in a paradoxical increase in [125I]IGF-I binding to the cell surface. The paradoxical increase occurred in the presence of excess insulin, indicating that unsaturated type I IGF receptors are not required to demonstrate this phenomenon. In a physiological salt solution, the order of affinity of the IGFBPs for IGF-I was IGFBP-3 greater than IGFBP-1 greater than IGFBP-2. These differences in affinity appear to account for the differences in IGF-I competition for binding that are seen when each of the three proteins is added. Thus, IGFBPs have the potential to alter the partitioning of IGF-I between cell surface-associated IGFBPs, membrane receptors, and the IGFBPs in extracellular fluids. The various forms of IGFBP affect IGF cell surface binding differently, and therefore, each may have distinct effects on IGF target cell actions.


Effect of nicomol on high density lipoprotein (HDL) subfractions, HDL2e and HDL3e, separated by electrophoresis.
High density lipoprotein (HDL) fractions were separated by dextran sulfate-Mg++ from sera of 5 healthy males before and after oral administration of a daily 1200 mg dose of Nicomol (2,2,6,6-tetrakis (nicotinoyloxymethyl) cyclohexanol; Cholexamin, Kyorin Pharmaceutical Co. Ltd.) for 2 weeks. The HDL fractions were further subdivided into HDL2e and HDL3e by Utermann's electrophoretic method on polyacrylamide gel containing lauric acid. These subfractions roughly corresponded to HDL2 and HDL3, respectively, which were separated by ultracentrifugation. Nicomol treatment increased the HDL2e/HDL3e ratio as is observed for the HDL2/HDL3 ratio, in addition to the increase in total HDL cholesterol concentration. The electrophoretic determination of HDL2e/HDL3e ratio in combination with HDL cholesterol level seemed to be clinically important in assessment of the alteration of HDL2 and HDL3 under physiological and pathological conditions.


Electromigration-induced propagation of nonlinear surface waves.
Due to the effects of surface electromigration, waves can propagate over the free surface of a current-carrying metallic or semiconducting film of thickness h(0). In this paper, waves of finite amplitude, and slow modulations of these waves, are studied. Periodic wave trains of finite amplitude are found, as well as their dispersion relation. If the film material is isotropic, a wave train with wavelength lambda is unstable if lambda/h(0)<3.9027 ..., and is otherwise marginally stable. The equation of motion for slow modulations of a finite amplitude, periodic wave train is shown to be the nonlinear Schrödinger equation. As a result, envelope solitons can travel over the film's surface.