Isovitexin Is a Direct Inhibitor of Staphylococcus aureus Coagulase.
Staphylococcus aureus (S. aureus) is a major pathogen that causes human pneumonia, leading to significant morbidity and mortality. S. aureus coagulase (Coa) triggers the polymerization of fibrin by activating host prothrombin, which then converts fibrinogen to fibrin and contributes to S. aureus pathogenesis and persistent infection. In our research, we demonstrate that isovitexin, an active traditional Chinese medicine component, can inhibit the coagulase activity of Coa but does not interfere with the growth of S. aureus. Furthermore, we show through thermal shift and fluorescence quenching assays that isovitexin directly binds to Coa. Dynamic simulation and structure-activity relationship analyses suggest that V191 and P268 are key amino acid residues responsible for the binding of isovitexin to Coa. Taken together, these data indicate that isovitexin is a direct Coa inhibitor and a promising candidate for drug development against S. aureus infection.


Multiple expression cassette exchange via TP901-1, R4, and Bxb1 integrase systems on a mouse artificial chromosome.
The site-specific excision of a target DNA sequence for genetic knockout or lineage tracing is a powerful tool for investigating biological systems. Currently, site-specific recombinases (SSRs), such as Cre or Flp recombination target cassettes, have been successfully excised or inverted by a single SSR to regulate transgene expression. However, the use of a single SSR might restrict the complex control of gene expression. This study investigated the potential for expanding the multiple regulation of transgenes using three different integrase systems (TP901-1, R4, and Bxb1). We designed three excision cassettes that expressed luciferase, where the luciferase expression could be exchanged to a fluorescent protein by site-specific recombination. Individual cassettes that could be regulated independently by a different integrase were connected in tandem and inserted into a mouse artificial chromosome (MAC) vector in Chinese hamster ovary cells. The transient expression of an integrase caused the targeted luciferase activity to be lost and fluorescence was activated. Additionally, the integrase system enabled the specific excision of targeted DNA sequences without cross-reaction with the other recombination targets. These results suggest that the combined use of these integrase systems in a defined locus on a MAC vector permits the multiple regulation of transgene expression and might contribute to genomic or cell engineering.


Role of microglial m1/m2 polarization in relapse and remission of psychiatric disorders and diseases.
Psychiatric disorders such as schizophrenia and major depressive disorder were thought to be caused by neurotransmitter abnormalities. Patients with these disorders often experience relapse and remission; however the underlying molecular mechanisms of relapse and remission still remain unclear. Recent advanced immunological analyses have revealed that M1/M2 polarization of macrophages plays an important role in controlling the balance between promotion and suppression in inflammation. Microglial cells share certain characteristics with macrophages and contribute to immune-surveillance in the central nervous system (CNS). In this review, we summarize immunoregulatory functions of microglia and discuss a possible role of microglial M1/M2 polarization in relapse and remission of psychiatric disorders and diseases. M1 polarized microglia can produce pro-inflammatory cytokines, reactive oxygen species, and nitric oxide, suggesting that these molecules contribute to dysfunction of neural network in the CNS. Alternatively, M2 polarized microglia express cytokines and receptors that are implicated in inhibiting inflammation and restoring homeostasis. Based on these aspects, we propose a possibility that M1 and M2 microglia are related to relapse and remission, respectively in psychiatric disorders and diseases. Consequently, a target molecule skewing M2 polarization of microglia may provide beneficial therapies for these disorders and diseases in the CNS.


Interplay between exogenous and endogenous factors in seasonal vegetation oscillations.
A fundamental question in ecology is whether vegetation oscillations are merely a result of periodic environmental variability, or rather driven by endogenous factors. We address this question using a mathematical model of dryland vegetation subjected to annual rainfall periodicity. We show that while spontaneous oscillations do not exist in realistic parameter ranges, resonant response to periodic precipitation is still possible due to the existence of damped oscillatory modes. Using multiple time-scale analysis, in a restricted parameter range, we find that these endogenous modes can be pumped by the exogenous precipitation forcing to form sustained oscillations. The oscillations amplitude shows a resonance peak that depends on model parameters representing species traits and mean annual precipitation. Extending the study to bistability ranges of uniform vegetation and bare soil, we investigate numerically the implications of resonant oscillations for ecosystem function. We consider trait parameters that represent species with damped oscillatory modes and species that lack such modes, and compare their behaviors. We find that the former are less resilient to droughts, suffer from larger declines in their biomass production as the precipitation amplitude is increased, and, in the presence of spatial disturbances, are likely to go through abrupt collapse to bare soil, rather than gradual, domino-like collapse.


Tuning the Hydrolytic Stability of Next Generation Maleimide Cross-Linkers Enables Access to Albumin-Antibody Fragment Conjugates and tri-scFvs.
We describe investigations to expand the scope of next generation maleimide cross-linkers for the construction of homogeneous protein-protein conjugates. Diiodomaleimides are shown to offer the ideal properties of rapid bioconjugation with reduced hydrolysis, allowing the cross-linking of even sterically hindered systems. The optimized linkers are exploited to link human serum albumin to antibody fragments (Fab or scFv) as a prospective half-life extension platform, with retention of antigen binding and robust serum stability. Finally, a triprotein conjugate is formed, by linking scFv antibody fragments targeting carcinoembryonic antigen. This tri-scFv is shown to infer a combination of greater antigen avidity and increased in vivo half-life, representing a promising platform for antibody therapeutic development.


Phototherapy of Alzheimer's Disease: Photostimulation of Brain Lymphatics during Sleep: A Systematic Review.
The global number of people with Alzheimer's disease (AD) doubles every 5 years. It has been established that unless an effective treatment for AD is found, the incidence of AD will triple by 2060. However, pharmacological therapies for AD have failed to show effectiveness and safety. Therefore, the search for alternative methods for treating AD is an urgent problem in medicine. The lymphatic drainage and removal system of the brain (LDRSB) plays an important role in resistance to the progression of AD. The development of methods for augmentation of the LDRSB functions may contribute to progress in AD therapy. Photobiomodulation (PBM) is considered to be a non-pharmacological and safe approach for AD therapy. Here, we highlight the most recent and relevant studies of PBM for AD. We focus on emerging evidence that indicates the potential benefits of PBM during sleep for modulation of natural activation of the LDRSB at nighttime, providing effective removal of metabolites, including amyloid-β, from the brain, leading to reduced progression of AD. Our review creates a new niche in the therapy of brain diseases during sleep and sheds light on the development of smart sleep technologies for neurodegenerative diseases.


Enamel growth rates of anterior teeth in males and females from modern and ancient British populations.
This study explored biological sex differences in the regional daily growth rates of human anterior enamel from modern and ancient populations in Britain. Maxillary permanent incisors (n = 80) and canines (n = 69) from Roman, Anglo-Saxon, Medieval, and Modern day populations were analyzed using histological methods. Daily secretion rates (DSRs) were collected for inner, mid, and outer regions of cuspal and lateral enamel. Modern day samples were of known sex, archeological individuals had sex determined using standard osteological methods. Variation in DSRs between the sexes, both between and within populations, was sought using parametric and nonparametric tests. When all samples were pooled, there was no significant difference between males and females. Similarly no significant differences in DSRs were identified between male and females within each population. When DSRs were compared between the populations, DSRs decreased from the more ancient to the more recent populations for males, and for females. More interpopulation differences were observed in males. This study presents evidence for the relative consistency of enamel DSRs between male and female groups within each British population. Interpopulation analyses found DSRs slowed significantly between Roman and modern day populations for both sexes, with male DSRs showing the greatest variation between populations.


Combination therapy for type 2 diabetes.
To discuss a rational approach to improvement of glycemic control in patients with type 2 diabetes mellitus with use of combination therapy. We review the mechanisms of action and clinical applications for the various antidiabetic agents alone and in various combinations. Relevant studies in the literature are reviewed. Although diet and exercise remain the cornerstones of treatment, in most patients with type 2 diabetes, pharmacologic agents are needed to achieve optimal glycemic control and likely reduce the incidence of microvascular and possibly macrovascular complications as well. Sulfonylureas have long been the foundation of oral pharmacologic therapy and provide adequate glycemic control for most patients for 5 to 10 years or longer. In the past, when treatment with sulfonylureas was no longer effective, insulin therapy was inevitable. With the approval of several new pharmacologic agents for the treatment of type 2 diabetes, however, the addition of one or more orally administered agents to sulfonylurea therapy or use of other oral combination therapy is rapidly evolving as a means of optimizing glycemic control. In many patients, combination therapy can delay the need to add or switch to insulin, or it can enhance glycemic control in patients already receiving insulin. In selected patients treated solely with insulin, discontinuation of insulin treatment and reinitiation of oral therapy may even be possible. Currently, four classes of orally administered antidiabetic agents are available for use in patients with type 2 diabetes: insulin secretagogues, biguanides, a-glucosidase inhibitors, and thiazolidinediones. By taking advantage of differing mechanisms of action, combination therapy is evolving as a means of optimizing glycemic control in patients in whom a single agent or insulin is inadequate. Combinations of orally administered agents can often delay the need for insulin or in combination with insulin aid in achieving glycemic goals. Continuing research will help optimize combination therapies even further.


[Mobile emergency care medical records audit: the need for Tunisian guidelines].
Objective: This study was designed to assess the quality of the Gabès (Tunisia) mobile emergency care medical records and propose corrective actions.Materials and methods: A clinical audit was performed at the Gabès mobile emergency care unit (SMUR). Records of day, night and weekend primary and secondary interventions during the first half of 2014 were analysed according to a data collection grid comprising 56 criteria based on the SMUR guidelines and the 2013 French Society of Emergency Medicine evaluation guide. A non-conformance score was calculated for each section.Results: 415 medical records were analysed. The highest non-conformance rates (48.5%) concerned the "specificities of the emergency medical record" section. The lowest non-conformance rates concerned the surveillance data section (23.4%). The non-conformance score for the medical data audit was 24%.Conclusion: This audit identified minor dysfunctions that could be due to the absence of local guidelines concerning medical records in general and more specifically SMUR. Corrective measures were set up in the context of a short-term and intermediate-term action plan.


Heightened Microbial Translocation Is a Prognostic Biomarker of Recurrent Tuberculosis.
Microbial translocation is a known characteristic of pulmonary tuberculosis (PTB). Whether microbial translocation is also a biomarker of recurrence in PTB is not known. We examined the presence of microbial translocation in a cohort of newly diagnosed, sputum smear, and culture positive individuals with drug-sensitive PTB. Participants were followed up for a year following the end of anti-tuberculosis treatment. They were classified as cases (in the event of recurrence, n = 30) and compared to age and gender matched controls (in the event of successful, recurrence free cure; n = 51). Plasma samples were used to measure the circulating microbial translocation markers. All the enrolled study participants were treatment naïve, HIV negative and with or without diabetes mellitus. Baseline levels of lipopolysaccharide (LPS) (P = .0002), sCD14 (P = .0191), and LPS-binding protein (LBP) (P < .0001) were significantly higher in recurrence than controls and were associated with increased risk for recurrence, whereas intestinal fatty acid binding protein (I-FABP) and Endocab showed no association. Receiver operating characteristic (ROC) curve analysis demonstrated the utility of these individual microbial markers in discriminating recurrence from cure with high sensitivity, specificity, and area under the curve (AUC). Recurrence following microbiological cure in PTB is characterized by heightened baseline microbial translocation. These markers can be used as a rapid prognostic tool for predicting recurrence in PTB.


The Ross procedure and valve-sparing root replacement procedures in the adult patient: do guidelines follow the evidence?
Prosthetic aortic valve replacements have long been the mainstay of valvular surgery due to their favorable outcomes and low operative complexity. Yet, mechanical valves require lifelong anticoagulation, whereas bioprosthetic valves increase the risk for earlier and more frequent reoperation. Alternative reconstructive techniques have been proposed to address these challenges. These include valve-sparing root replacement procedures if the native aortic valve can be salvaged, and the Ross procedure, which nearly eliminates prosthetic valve-related thromboembolism, anticoagulation-related hemorrhage and endocarditis. Both procedures are technically more complex and thus subject to surgeons' volume and expertise compared to conventional aortic valve replacements. However, they are associated with more favorable outcomes compared to aortic valve replacements if performed by experienced surgeons, especially in younger patients. Nevertheless, despite the growing high-quality literature supporting both procedures, existing multi-society guidelines fail to acknowledge the strength of evidence in support of valve-sparing root replacement procedures and the Ross procedure. In this review, we summarize the existing long-term evidence for the use of each procedure, describe the current guidelines for the treatment of aortic valve pathology, and propose the reevaluation of guidelines based on the available clinical evidence.


Transverse myelitis associated with Mycoplasma pneumoniae infection.
A 14-year-old boy developed acute transverse myelitis with severe abdominal pain, bladder dysfunction, weakness, and sensory loss of the lower extremities. Magnetic resonance imaging revealed a segmental expanded central edema affecting parts of the spinal cord, including the caudal medulla oblongata. Antibody response to Mycoplasma pneumoniae was negative in microparticle agglutination assays (1:40 in the acute serum and 1:160 in the convalescent serum) and complement fixation tests (1:20 and 1:10). However, analysis of acute-phase serum revealed a specific IgA and IgG response but no IgM response. Detection of M. pneumoniae in the cerebrospinal fluid by nested polymerase chain reaction and in nasopharyngeal aspirate by culture confirmed an M. pneumoniae infection. Treatment with doxycycline (100 mg daily) was started on the second day after admission to the hospital and continued for 14 days; the patient recovered completely and was discharged 20 days after onset of the disease, with no signs of neurological deficits.


Bypass enteropathy. Intestinal and systemic manifestations following small-bowel bypass.
Many manifestations following jejunoileal bypass are due to chronic inflammation of the excluded bowel rather than short bowel malabsorption. Diarrhea, abdominal distention, and gas-fluid levels were common diagnostic features of "bypass enteropathy." Exploration showed the bypassed bowel to be dilated, with serosal inflammation and pneumatosis cystoides intestinalis. The bypassed loops contained a fecal flora and the mucosa demonstrated nonspecific chronic inflammatory changes. Exudative protein losses were noted. Systemic complications of bypass enteropathy were similar to other inflammatory diseases of the bowel. Improvement following treatment with metronidazole or after dismantling of the bypass suggested that bacterial byproducts originating in the excluded bowel were causally related.


Ocular abnormalities in Apert syndrome: genotype/phenotype correlations with fibroblast growth factor receptor type 2 mutations.
Apert syndrome, a disorder of craniosynostosis, syndactyly, and other craniofacial malformations, is caused by point mutations (Ser252Trp or Pro253Arg) in the fibroblast growth factor receptor 2 gene. This study's goal was to determine ophthalmic phenotype/genotype correlations in patients with either mutation. A retrospective chart review of demographic and ophthalmologic data was performed for 18 children carrying either the S252W (11) or the P253R (7) mutation. Fisher exact tests were performed to determine significance of variable phenotypes between the two mutation groups. In the P253R group, 85% had strabismus (14% required surgery), 71% had ptosis, 43% had amblyopia, 14% had nasolacrimal duct obstruction, 14% had myopia, 14% had hyperopia, and 14% had astigmatism. In the S252W group, 91% had strabismus (64% required surgery), 73% had ptosis, 73% had amblyopia, 100% had nasolacrimal duct obstruction, 36% had myopia, 9% had hyperopia, and 82% had astigmatism. Overall, S252W and P253R groups showed significantly different numbers of patients with strabismus requiring surgery (p = 0.039), superior rectus muscle underaction (p = 0.024), nasolacrimal duct obstruction (p = 0.0002), and astigmatism (p = 0.005). Compared with patients with the P253R mutation, Apert syndrome patients with the S252W mutation may have more severe ocular phenotypes with a higher likelihood of developing strabismus, especially vertical deviation. They also are more likely to develop astigmatic refractive errors and tearing secondary to nasolacrimal system anomalies.


Interface Engineering of Gold Nanoclusters for CO Oxidation Catalysis.
Catalysts based on atomically precise gold nanoclusters serve as an ideal model to relate the catalytic activity to the geometrical and electronic structures as well as the ligand effect. Herein, we investigate three series of ligand (thiolate)-protected gold nanoclusters, including Au38(SR)24, Au36(SR')24, and Au25(SR″)18, with a focus on their interface effects using carbon monoxide (CO) oxidation as a probe reaction. The first comparison is within each series, which reveals the same trend for the three series that, rather than the bulkiness of carbon tails as commonly thought, the steric hindrance of ligands at the interface between the thiolate, Au, and CeO2 inhibits CO adsorption onto Au sites and hence adversely affects the activity of CO oxidation. The second comparison is between the sets Au38(SR)24 and Au36(SR')24 of nearly the same size, which reveals that the Au36(SR')24 nanoclusters (with face centered cubic structure) are not sensitive to thermal pretreatment conditions, whereas the Au38(SR)24 catalysts (icosahedral structure) are and an optimum activity is observed at a pretreatment temperature of 150 °C. Overall, the atomically precise Au n(SR) m nanoclusters have revealed unprecedented details on the catalytic interface and atomic structure effects. It is hoped that such insights will benefit the ultimate goal of catalysis in future design of enzymelike catalysts for environmentally friendly green catalysis.


Mood Profiling in Singapore: Cross-Cultural Validation and Potential Applications of Mood Profile Clusters.
Mood profiling is a popular method of quantifying and classifying feeling states. Previous research has identified several novel mood profiles in predominantly Western English-speaking populations (Parsons-Smith et al., 2017), and replicated the findings in the domain of sport and exercise (Quartiroli et al., 2018; Terry and Parsons-Smith, 2019). The aim of the current study was to investigate if six hypothesized clusters of mood responses were evident in a population of English-speaking sport and non-sport participants in Singapore. A seeded k-means cluster analysis was applied to the mood responses of 1,444 participants (991 male, 440 female, 13 unspecified; aged 18-65 years) who completed the Brunel Mood Scale (BRUMS; Terry et al., 1999, 2003a). The six hypothesized mood profiles (i.e., iceberg, inverse Everest, inverse iceberg, shark fin, submerged, and surface profiles) were identified clearly. Chi-squared analyses showed unequal distribution of the profiles by gender, age group, ethnicity, education level, and sport participation. Findings support the cross-cultural generalizability of the six mood profiles in English-speaking sport and non-sport samples in Singapore and contribute to investigation into the antecedents, correlates, and consequences of each mood profile.


Methane-Oxidizing Bacteria Shunt Carbon to Microbial Mats at a Marine Hydrocarbon Seep.
The marine subsurface is a reservoir of the greenhouse gas methane. While microorganisms living in water column and seafloor ecosystems are known to be a major sink limiting net methane transport from the marine subsurface to the atmosphere, few studies have assessed the flow of methane-derived carbon through the benthic mat communities that line the seafloor on the continental shelf where methane is emitted. We analyzed the abundance and isotope composition of fatty acids in microbial mats grown in the shallow Coal Oil Point seep field off Santa Barbara, CA, USA, where seep gas is a mixture of methane and CO2. We further used stable isotope probing (SIP) to track methane incorporation into mat biomass. We found evidence that multiple allochthonous substrates supported the rich growth of these mats, with notable contributions from bacterial methanotrophs and sulfur-oxidizers as well as eukaryotic phototrophs. Fatty acids characteristic of methanotrophs were shown to be abundant and 13C-enriched in SIP samples, and DNA-SIP identified members of the methanotrophic family Methylococcaceae as major 13CH4 consumers. Members of Sulfuricurvaceae, Sulfurospirillaceae, and Sulfurovumaceae are implicated in fixation of seep CO2. The mats' autotrophs support a diverse assemblage of co-occurring bacteria and protozoa, with Methylophaga as key consumers of methane-derived organic matter. This study identifies the taxa contributing to the flow of seep-derived carbon through microbial mat biomass, revealing the bacterial and eukaryotic diversity of these remarkable ecosystems.


[Delayed clinical outcomes of coronary syndrome X: results of 15 year-long monitoring].
Clinical and pathomorphological outcomes of coronary syndrome X in 40 patients with intact subepicardial coronary arteries are analysed based on the results of 15 year-long monitoring. Primary examination revealed microvascular lesions in the coronary vessels in the form of idiopathic microangiopathy and plastic cardiomyocyte insufficiency confirmed by endomyocardial biopsy studies. The commonest undesirable outcomes after 15 years were myocardial infarction (7.5%), cerebral stroke (10%), persistent cardiac rhythm disturbance (15.4), and sudden cardiac death (17.5%). Sub-epicardial coronary arteries remained unaltered in 82.5% of the patients although they suffered atherosclerosis of peripheral arteries. It appears that coronary syndrome X is a specific microvascular form of coronary heart disease (MCHD) always coupled to systemic vascular pathology. The main consequence of MCHD is remodeled metabolism and biochemical changes contributing to multifocal systemic atherosclerosis. MCHD is diagnosed 10-15 years earlier than classical CHD. At the late stage of pathomorphogenesis, MCHD may remain a self-contained nosological form comparable with atherosclerotic CHD in terms of severity and clinical manifestations. MCHD is characterized by systemic atherosclerosis of peripheral arteries and (in 1/5 of the patients) by coronary atherosclerosis.


Consecutive alkene cross-metathesis/oxonium ylide formation-rearrangement: synthesis of the anti-HIV agent hyperolactone C.
Alpha-diazo-beta-ketoesters bearing allylic ether functionality undergo highly stereoselective Ru-carbene-catalyzed alkene cross-metathesis followed by Rh(2)(OAc)(4)-catalyzed oxonium ylide formation/[2,3] sigmatropic rearrangement in a one-flask operation and in a highly diastereoselective manner. The methodology has been demonstrated in a concise synthesis of the anti-HIV agent hyperolactone C.


A day rehabilitation stroke program.
An innovative approach to the rehabilitation of the stroke patient was initiated at Riverside Methodist Hospital to accommodate an increasing number of patients. Patients spend six hours a day several days a week attending a day rehabilitation program at which all necessary therapies are provided. A year-end analysis of the program substantiates the original hypothesis that stroke patients would show significant improvement with treatment in a specialized day rehabilitation facility.


Out-of-hospital sepsis recognition by paramedics improves the course of disease and mortality: A single center retrospective study.
Early recognition of sepsis and a prompt initiation of goal-directed therapy is important for sepsis survival. Little is known about the impact of early recognition of sepsis in the out-of-hospital setting when paramedics are the 1st medical professionals arriving on the scene. To characterize the impact of sepsis recognition by paramedics in the 1st out-of-hospital contact and to establish a predictive model by combining preclinical patient characteristics. In this retrospective single-center cohort study, we included a total of 263 patients diagnosed with sepsis after admission to the emergency department and correlated them to the emergency medical protocols of the paramedics who have seen the patient out-of-hospital. Only 25 patients were correctly diagnosed by paramedics out-of-hospital. If sepsis was diagnosed, the median time to antibiotic administration was significantly lower (136.50 min compared to 206.98 min, p = 0.0069) and mortality was reduced from 22.8% to 8% (p = 0.0292). We have identified predictors for prognosis and calculated a predictive model with a modified quick Sepsis-related Organ Failure Assessment (qSOFA) score, which fits the needs for out-of-hospital usage and results in a better discrimination of vitally threatened patients (receiver operating characteristic (ROC) area under curve (AUC) of 0.641 compared to 0.719), as compared to the standard qSOFA. Sepsis recognition by paramedics at the 1st out-of-hospital contact significantly reduces sepsis mortality. The qSOFA and modified qSOFA are suitable tools for sepsis recognition, and have an impact on mortality and disease management when used.


Aortic valve replacement in the calcified small aortic root by hemitranslocation of the valve.
An alternative technique of aortic valve replacement is described for a small aortic root with a severe large calcific degeneration of the supraaortic area at the noncoronary sinus. This technique is used when Nicks or Manouguian procedures are not applicable.


Access to healthcare and alternative health-seeking strategies among undocumented migrants in Denmark.
As in many European countries, undocumented migrants in Denmark have restricted access to healthcare. The aim of this study is to describe and analyse undocumented migrants' experiences of access to healthcare, use of alternative health-seeking strategies; and ER nurses' experiences in encounters with undocumented migrants. Qualitative design using semi-structured interviews and observations. The participants included ten undocumented South Asian migrants and eight ER nurses. Undocumented migrants reported difficulties accessing healthcare. The barriers to healthcare were: limited medical rights, arbitrariness in healthcare professionals' attitudes, fear of being reported to the police, poor language skills, lack of network with Danish citizens, lack of knowledge about the healthcare system and lack of knowledge about informal networks of healthcare professionals. These barriers induced alternative health-seeking strategies, such as self-medication, contacting doctors in home countries and borrowing health insurance cards from Danish citizens. ER nurses expressed willingness to treat all patients regardless of their migratory status, but also reported challenges in the encounters with undocumented migrants. The challenges for ER nurses were: language barriers, issues of false identification, insecurities about the correct standard procedures and not always being able to provide appropriate care. Undocumented migrants face formal and informal barriers to the Danish healthcare system, which lead to alternative health-seeking strategies that may have adverse effects on their health. This study shows the need for policies and guidelines, which in accordance with international human rights law, ensure access to healthcare for undocumented migrants and give clarity to healthcare professionals.


Ignimbrite textural properties as determinants of endolithic colonization patterns from hyper-arid Atacama Desert.
This study explores the photosynthetic microbial colonization of rhyolitic ignimbrites in Lomas de Tilocalar, a hyper-arid region of the Atacama Desert, Chile. Colonization appeared in the form of a green layer a few millimeters beneath the ignimbrite surface. Some ignimbrite rocks revealed two distinct micromorphological areas of identical mineralogical and chemical composition but different textural properties. According to texture, colonization patterns varied in terms of the extension and depth of colonization. The diversity of photosynthetic microorganisms was assessed by denaturing gradient gel electrophoresis (DGGE) of the 23S rRNA gene and by generating clone libraries of the 16S rRNA gene. We observed a low diversity of photosynthetic microorganisms colonizing the ignimbrite microhabitat. Most rRNA gene sequences recovered greatly resembled those of Chroococcidiopsis hypolith clones from arid deserts. These results point to highly restrictive conditions of the hyper-arid Atacama Desert conditioning the diversity of cyanobacteria, and suggest that microbial colonization and composition patterns might be determined by the microscale physico-chemical properties of the ignimbrite rocks.


A novel supramolecular metallogel-based high-resolution anion sensor array.
A novel anion sensor array based on supramolecular metallogels has been developed. It could accurately identify CN(-), SCN(-), S(2-) and I(-) in water. Interestingly, this sensor array is based on a novel design approach termed "competitive coordination control AIE mode" to develop anion-responsive gels which need only one synthesized gelator G1.


The role of microRNAs in congenital heart disease.
Congenital heart diseases (CHDs) are the leading inherited cause of perinatal and infant mortality. CHD refers to structural anomalies of the heart and blood vessels that arise during cardiac development and represents a broad spectrum of malformations, including septal and valve defects, lesions affecting the outflow tract and ventricules. Advanced treatment strategies have greatly improved life expectancy and led to expanded population of adult patients with CHD. Thus, a better understanding of the pathogenesis and molecular mechanisms underlying CHDs is essential to improve the diagnosis and prognosis of patients. The etiology of CHD is largely unknown, genetic and environmental factors may contribute to the disease. In addition to the mutations affecting genomic DNA, epigenetic changes are being increasingly acknowledged as key factors in the development and progression of CHDs. The posttranscriptional regulation of gene expression by microRNAs (miRs) controls the highly complex multi-cell lineage process of cardiac tissue formation. In recent years, multiplex experimental models have provided evidence that changes in expression levels of miRs are associated with human cardiovascular disease, including CHD. The newly described correlations between miRs and heart development suggest the potential importance of miRs as diagnostic markers in human cardiovascular diseases. In the future, more intensive research is likely to be carried out to clarify their contribution to personalized management and treatment of CHD patients. In this paper, we discuss the current knowledge on the causative role of miRs in cardiac development and CHDs.


Intensity and duration of salinity required to form adaptive response in C4 halophyte Kochia prostrata (L.) Shrad.
Plant adaptation to salinity is a highly multifaceted process, harnessing various physiological mechanisms depending on the severity and duration of salt stress. This study focuses on the effects of 4- and 10-day treatments with low (100 mM NaCl) and moderate (200 mM NaCl) salinity on growth, CO2/H2O gas exchange, stomatal apparatus performance, the efficiency of photosystems I and II (PS I and II), content of key C4 photosynthesis enzymes, and the accumulation of Na+, K+, and proline in shoots of the widespread forage C4 halophyte Kochia prostrata. Our data show that 4 days of low salinity treatment resulted in a decrease in biomass, intensity of apparent photosynthesis, and cyclic electron transport around PS I. It was accompanied by an increase in transpiration and Rubisco and PEPC contents, while the Na+ and proline contents were low in K. prostrata shoots. By the 10th day of salinity, Na+ and proline have accumulated; PS I function has stabilized, while PS II efficiency has decreased due to the enhanced non-photochemical quenching of chlorophyll fluorescence (NPQ). Thus, under low salinity conditions, Na+ accumulated slowly and the imbalance between light and dark reactions of photosynthesis was observed. These processes might be induced by an early sodium signaling wave that affects cellular pH and ion homeostasis, ultimately disturbing photosynthetic electron transport. Another adaptive reaction more "typical" of salt-tolerant species was observed at 200 mM NaCl treatment. It proceeds in two stages. First, during the first 4 days, dry biomass and apparent photosynthesis decrease, whereas stomata sensitivity and dissipation energy during dark respiration increase. In parallel, an active Na+ accumulation and a decreased K+/Na+ ratio take place. Second, by the 10th day, a fully-fledged adaptive response was formed, when growth and apparent photosynthesis stabilized and stomata closed. Decreased dissipation energy, increased WUE, stabilization of Rubisco and PEPC contents, and decreased proline content testify to the completion of the adaptation and stabilization of the physiological state of plants. The obtained results allowed us to conclude that the formation of a full-fledged salt-tolerant response common for halophytes in K. prostrata occurs by the 10th day of moderate salinity.


Klippel Trenaunay Syndrome: A Case Report in an Adolescent Nigerian Boy.
This is to report a case of Klippel Trenauay Weber syndrome in a fifteen year old Nigerian boy. This is a rare syndrome and it is the first case to be reported in UCTH Calabar. Product of a full term uneventful pregnancy, delivered to non-consanguineous apparently healthy parents. At birth was noted to gradually develop swelling on the right leg, worse at the right foot. There was crossed hemi-hypertrophy with right leg bigger than the left. As child grew symptoms worsened, parents separated and eventually he was abandoned to the streets. He presented at University of Calabar Teaching Hospital for medical care at the age of fifteen years with lymphatic obstruction, persistent foul smelling drainage, lipodermatosclerosis of right foot as well psycho-social and financial constraints. The diagnosis was made with x-rays and Doppler studies of the lower limb vessels. He is currently being managed conservatively with compression dressings on the affected limbs, Antibiotics for the infection and analgesics. De-bulking surgery is being anticipated at this time. This is a case of KTWS presenting in adolescence and due to its rarity in Nigeria, this report is to increase awareness.


Spreading depression induces depletion of MAP2 in area CA3 of the hippocampus in a rat unilateral carotid artery occlusion model.
Traumatic brain injury (TBI) induces neuronal cell loss in area CA3 of the hippocampus. However, it has not yet been established why traumatic injury of the cortex induces neuronal damage in more remote areas. Spreading depression (SD) may be one potential mechanism for this pathophysiology. The present study evaluated whether SD on the cortex evokes a pathological change in the hippocampus. Forty-two Fisher rats were assigned to four groups: Group I: sham operation (n = 7), Group II: right carotid occlusion (UO) for 7 days (n = 7), Group III: repeated induction of SD by KCl application on dura for 7 days (n = 7), Group III' for 3 h (n = 7), Group IV: SD induction and UO for 7 days (n = 14) Group IV' for 3 h (n = 7). In 5 out of 7 animals in Groups III' and IV', cerebral blood flow (CBF) was monitored using laser Doppler flowmetry for 3 h during the passage of SD. The brains were processed for immunohistochemical analysis of microtubule-associated protein 2 (MAP2). Reactive hyperemia induced by SD was not significantly suppressed by right carotid occlusion (194 +/- 25% and 181 +/- 42% UO in Groups III and IV, respectively). In 6 out of 7 animals in a 7-day model of Group IV, and 3 animals in a 7-day model of Group III, MAP2 depletion in the CA3 area of the hippocampus (partly including CA2) was observed, although no change in the hippocampus was observed in other groups. In conclusion, SD in combination with UO yielded reproducible lesions in CA3. Neuronal injury in the hippocampus after brain trauma may be attributable to SD in combination with the blood flow restriction.


[Subaxial Cervical Spine Injuries: Treatment Recommendations of the German Orthopedic and Trauma Society].
In a consensus process during four sessions in 2016, the working group "lower cervical spine" of the German Society for Orthopedic and Trauma Surgery (DGOU), formulated "Therapeutic Recommendations for the Lower Cervical Spine", taking into consideration the current literature. Therapeutic goals are a permanently stable, painless cervical spine and the protection against secondary neurologic damage while retaining the greatest possible amount of motion and spinal profile. Due to its ease of use and its proven good reliability, the AOSpine classification for subaxial cervical injuries should be used. The Canadian C-Spine Rule is recommended as a clinical decision rule whether to perform imaging or not. If a structural or unstable injury is suspected by patient history or clinical findings, a spiral CT scan of the cervical spine is the favoured diagnostic modality. Conventional X-ray is reserved for patients in whom there is no "dangerous mechanism of injury". MR imaging is recommended in case of unexplained neurologic deficit, prior to closed reduction and open posterior surgery and to exclude disco-ligamentous injuries. Urgency of MR imaging depends on the specific findings. CT angiography is recommended in higher-grade facet joint injuries or in the presence of vertebra-basilar symptoms. Flexion-extension imaging is recommended only as a physician-guided dynamic fluoroscopy, when an unstable lesion is still suspected. The therapeutic strategy is mainly dependent on morphologic criteria, which are described using the AOSpine classification. A0-injuries are treated conservatively. A1- and A2-injuries are treated conservatively in the majority of cases, and in single cases a gross kyphotic deformity might indicate surgical stabilisation. A3-injuries do indicate a surgical therapy in the majority of cases, but certain cases might be treated conservatively. A4-fractures as well as B- and C-type injuries are to be treated surgically. Most injuries can be treated by anterior plate stabilisation with interbody support; when a complete burst fracture is present, corpectomy and vertebral body replacement is necessary. In certain cases, an additive posterior or pure posterior instrumentation might be possible or even mandatory. In most of these cases, lateral mass screws are sufficient; when pedicle screws are applied in C3 to C6, a 3D-navigation system is recommended. Injuries in an ankylosing spine (M3-modifier) should be treated preferably from posterior with long-segment instrumentation.


Outcomes following laparoscopic versus open major hepatectomy for hepatocellular carcinoma in patients with cirrhosis: a propensity score-matched analysis.
Laparoscopic major hepatectomy (LMH) for hepatocellular carcinoma (HCC) in patients with cirrhosis remains controversial due to limited reports in the literature. This study analyzed the perioperative and oncological outcomes of LMH for HCC with cirrhosis compared with open major hepatectomy (OMH). A retrospective analysis of patients with cirrhosis who underwent major hepatectomy for HCC between January 2015 and January 2017 was performed. Patients were divided into the LMH group and the OMH group. Short-term and oncological outcomes were compared before and after 1:1 propensity score matching (PSM). A total of 103 HCC patients who received major liver resection were enrolled. There were 36 (35.0%) patients in the LMH group and 67 (65.0%) patients in the OMH group. After 1:1 PSM, well-matched 32 patients in each group were evaluated. Significant differences were observed in operative time (median, 255 vs. 200 min, p < 0.001) and Pringle time (median, 50 vs. 30 min, p < 0.001) between two groups. The blood loss and transfusion requirement were comparable in two groups. The rate of overall postoperative complications did not differ between two groups, while the incidence of ascites in the LMH group was significantly less than OMH group (9.4 vs. 31.3%, p = 0.030). The oncological outcomes between the two groups were comparable with regard to 2-year overall survival (85.7 vs. 86.7%, p = 0.694) and disease-free survival (72.9 vs. 81.5%, p = 0.990), respectively. LMH for HCC patients with liver cirrhosis showed comparable results in terms of postoperative morbidity and oncological outcomes compared with traditional open procedure. LMH may serve as a safe and feasible alternative for selected HCC patients with cirrhosis.


Reversal of low-level resistance to Bacillus sphaericus in a field population of the southern house mosquito (Diptera:Culicidae) from an urban area of Recife, Brazil.
A larval population of Culex quinquefasciatus Say from an urban area (Coque) of Recife, Brazil, submitted to selection with Bacillus sphaericus Neide for a 26-mo trial, was 10 times less susceptible to B. sphaericus and slightly more susceptible to Bacillus thuringiensis israelensis, compared with untreated populations. The low-level resistance to B. sphaericus was unstable in the absence of selection pressure. The LC50 of B. sphaericus to the Coque population declined gradually and attained a susceptibility level similar to that observed in a laboratory control colony 16 mo after the treatment period was interrupted. In parallel to the recovery of B. sphaericus susceptibility. Coque larvae also were as susceptible as laboratory larvae to B. thuringiensis israelensis.


[Microorganisms of special herb-glycosidases and their fermentation, enzyme properties].
Herb-glycosides are main active elements of Zhongcaoyao (Chinese traditional medicines, Chinese medical herbs). However, the herb-glycoside structures are not optimal active structure for the human bodies. After orally taken up, the herb-glycosides of Zhongcaoyao could be changed into other more active structures by the digestive system such as enzymes and intestinal microorganisms; then degraded and absorbed in the human body and play the real role of pharmic effect; but only a small amount could be changed and controlled by circadian state of the human body. If this biochange of herb-glycosides to more active structures in vivo was finished in vitro, it is very useful for the development of the Chinese traditional medicines, new plant medicines, health food, and function cosmetics. To biotransformate herb-glycosides to more active structure, this paper introduced the studies of author's team on the new microorganism isolation of the special herb-glycosidases and enzyme fermentation, the special enzyme purification and characterization.


[How to use microbiological diagnostic tests in a hospital setting].
Microbiological cultures provide essential information to guide the antibiotic therapy. However, their results might be misleading for physicians and drive useless treatment, sometimes harmful for patients. Recommendations highlight the importance of clinical signs in order to take into account the pre-test probability when interpreting the results. This combination will improve the predictive value of microbiological tests. The sampling strategy is also important to avoid an overuse of these tests but also misleading results through a reduction of contaminants.


Gold particle interaction in regular arrays probed by surface enhanced Raman scattering.
Lithographically designed two-dimensional arrays consisting of gold nanoparticles deposited on a smooth gold film are used as substrate to examine the SERS effect of the trans-1,2-bis (4-pyridyl) ethylene molecule. These arrays display two plasmon bands instead of the single one observed for the same arrays of particles but deposited on indium tin oxide coated glass. Laser excitation within the short wavelength band does not bring about any SERS spectrum, while excitation within the long wavelength band yields SERS spectra with a gain per molecule rising up to 10(8). The simultaneous investigation of extinction and Raman spectra of arrays exhibiting various topography parameters enables us to suggest an interpretation for both the occurrence of the two plasmon resonances and for the high Raman enhancement. We suggest to assign the short wavelength band to a plasmon wave propagating at the gold glass interface and the long wavelength one to an air/gold surface plasmon mode modified by particle-particle interaction.


[Serum gastrin levels in patients with changes of gastric or duodenal mucosa (author's transl)].
The mean concentration of gastrin in serum was determined in healthy fasting persons (n = 27), it amounted to 56.8 pg/ml (SD = 19.8 PG/ML). The values of gastrin in serum of patients, who were grouped by endoscopicbioptic criteria of antral mucosa and who exceptionally showed diffuse inflammation of gastric mucosa, amounted to 73.2 pg/ml in patients with mild superficial gastritis (n = 24), to 73.4 pg/ml in those with severe superficial gastritis (n = 55), to 82.3 pg/ml in patients with chronic atrophic gastritis (n = 11) and to 70.7 pg/ml in those with chronic atrophic gastritis and intestinal metaplasia (n = 17). The concentration of serum gastrin in patients with additional pathological processes of gastric or duodenal mucosa was also determined. Patients with gastric resection according to Billroth II (n = 15) revealed gastrin values of 47.8 pg/ml, those with duodenal ulcer (n = 5) of 58.5 pg/ml, with gastric ulcer (n = 50) of 61.3 pg/ml, with polyps in stomach (n = 10) of 109.6 pg/ml and with neoplasms of the stomach (n = 27) of 77.7 pg/ml. Gastrin values were not correlated to age or sex. The difference between the mean gastrin concentrations of the mentioned groups of patients however is not marked enough and the range of values is too wide to characterize those groups by specific gastrin levels. The determination of gastrin in serum of fasting patients is not helpful for diagnosis of gastritis without antibodies to intrinsic factor or for diagnosis of certain localized pathological conditions in stomach or duodenum obviously.


Mood dysregulation and affective instability in emerging adults with childhood maltreatment: An ecological momentary assessment study.
Childhood maltreatment increases risk for mood, anxiety, substance use and personality disorders and is associated with alterations in structure, function and connectivity of brain regions involved in emotional regulation. We sought to assess whether maltreatment was specifically associated with disturbances in positive or negative mood regulation. Ecological momentary ratings were collected with a wristwatch-like device with joy-stick (Seiko ecolog) approximately six times per day over a week in 60 unmedicated participants (22 control, 38 maltreated, 18-25 years old). Forty-five percent of maltreated subjects had a history of major depression but all were currently euthymic. Principal component analysis with varimax rotation was used to provide orthogonal measures of positive and negative valence, which were analyzed for indices of variability, circadian rhythmicity and persistence, using linear and non-linear hierarchical modeling and Hurst analysis. Groups did not differ in mean levels of positive or negative affect. Maltreated subjects had increased variability and circadian and hemicircadian abnormalities in ratings of positive but not negative affect. Conversely, they had higher estimated Hurst exponents for negative but not positive affect ratings indicating a greater degree of persistence. Abnormalities in variability, rhythmicity and persistence were present in both maltreated subjects with and without histories of major depression. These findings suggest that both positive and negative valence systems may be dysregulated in individuals with childhood maltreatment. However the nature of the dysregulation appears to differ fundamentally in these domains, as positive mood ratings were more variable and negative ratings more persistent.


Functionalized PLA-PEG nanoparticles targeting intestinal transporter PepT1 for oral delivery of acyclovir.
Targeting intestinal di- and tri-peptide transporter PepT1 with prodrugs is a successful strategy to improve oral drug bioavailability, as demonstrated with valacyclovir, a prodrug of acyclovir. The aim of this new drug delivery strategy is to over-concentrate a poorly absorbed drug on the intestinal membrane surface by targeting PepT1 with functionalized polymer nanoparticles. In the present study, poly(lactic acid)-poly(ethylene glycol)-ligand (PLA-PEG-ligand) nanoparticles were obtained by nanoprecipitation. A factorial experimental design allowed us to identify size-influent parameters and to obtain optimized ≈30nm nanoparticles. Valine, Glycylsarcosine, Valine-Glycine, and Tyrosine-Valine were chemically linked to PLA-PEG. In Caco-2 cell monolayer model, competition between functionalized nanoparticles and [3H]Glycylsarcosine, a strong substrate of PepT1, reduced [3H]Glycylsarcosine transport from 22 to 46%. Acyclovir was encapsulated with a drug load of ≈10% in valine-functionalized nanoparticles, resulting in a 2.7-fold increase in permeability as compared to the free drug. An in vivo pharmacokinetic study in mice compared oral absorption of acyclovir after administration of 25mg/kg of valacyclovir, free or encapsulated acyclovir in functionalized nanoparticles. Acyclovir encapsulation did not statistically modify AUC or Cmax, but increased t1/2 and MRT 1.3-fold as compared to free acyclovir. This new strategy is promising for poorly absorbed drugs by oral administration.


Transcriptional arrest of yeast RNA polymerase II by Escherichia coli rho protein in vitro.
A promoter-independent assay utilizing poly(dC)-tailed DNA templates has revealed that Saccharomyces cerevisiae whole-cell extracts can be proficient for transcription by the endogenous yeast RNA polymerase II as well as for correct 3'-end RNA processing. Our attempts to examine the fate of polymerase II itself were inconclusive, because only trace transcription products corresponded to the expected size of terminated RNA species. Transcription in our processing-proficient extract was thus insufficient to cause termination. To test our system with a known, albeit heterologous, signal, we examined a dC-tailed template carrying the E. coli rho-dependent termination signal trp t' in the yeast extract. Transcripts from this template were not susceptible to processing, but addition of rho protein resulted in two distinct truncated transcripts that could not be chased by excess unlabeled nucleotides. These RNA species thus represented stably paused or terminated polymerase II products, and their absence when a mutated unresponsive trp t' template was used affirmed that they were due to the effects of rho. E. coli RNA polymerase added to a yeast extract pretreated with alpha-amanitin was also halted by rho at these same two sites. A mutated rho protein, while only partly defective with E. coli polymerase, failed to provoke arrest when transcription was carried out by RNA polymerase II. Thus, functional rho and its cognate site, trp t', appear necessary and sufficient to elicit the production of truncated transcripts by RNA polymerase II in a yeast whole-cell extract. The ability of rho to halt the eukaryotic enzyme strengthens the likelihood that a rho-like helicase may be involved in RNA polymerase II transcription termination.


ICI182,780 induces p21Waf1 gene transcription through releasing histone deacetylase 1 and estrogen receptor alpha from Sp1 sites to induce cell cycle arrest in MCF-7 breast cancer cell line.
We used the estrogen-responsive MCF-7 breast cancer cell line as a relevant model to study the anti-proliferative effects of ICI182,780 and identified the negative cell cycle regulator p21Waf1 as a specific target of ICI182,780. Furthermore, silencing of the p21Waf1 expression by small interfering RNA overcame the G0/G1 cell cycle arrest induced by ICI182,780, suggesting that the induction of p21Waf1 expression has a direct role in mediating the ICI182,780-induced G0/G1 arrest. We further demonstrated that the induction of p21Waf1 by ICI182,780 is mediated at transcriptional and gene promoter levels through the proximal Sp1 sites located near the transcription start site. Co-immunoprecipitation, DNA "pull-down," and chromatin immunoprecipitation experiments together showed that in cycling cells, estrogen receptor alpha and histone deacetylase 1 (HDAC1) are recruited to the proximal Sp1 sites of the promoter to repress p21Waf1 expression. In the presence of ICI182,780, estrogen receptor alpha and HDACs are dissociated from Sp1, resulting in increased histone acetylation and de-repression of the p21Waf1 promoter and induction of p21Waf1 expression. The fact that p21Waf1 expression is normally repressed by HDAC activity in cycling cells is further demonstrated by the finding that p21Waf1 transcription can be induced by the silencing of HDACs with small interfering RNA or treatment with HDAC inhibitors.


Hemangiopericytomas of the spinal canal. Report of four cases and review of literature.
The Authors report four cases of spinal hemangiopericytomas. The diagnosis has been ascertained by electron microscopy. Despite the malignant nature, the association of surgery and radiotherapy is interesting in that it prolongs the survival rate. Clinical, neuroradiological, microscopic and ultrastructural features of intraspinal hemangiopericytomas are evaluated in the light of the review of the relevant literature.


[Respiratory distress. New Perspectives to lung edema treatment].
Acute respiratory distress syndrome (ARDS) is a life threatening condition associated with great morbidity and mortality. it is characterized initially by accumulation of fluid in the alveolar space that impairs alveolar oxygen exchange. Eventually, this syndrome leads to multiorgan failure. Therefore, rapid edema clearance has generally been associated with better outcome in patients with acute respiratory distress syndrome. Clearance of alveolar fluid is driven predominantly by active Na+ transport out of the alveolar space, mediated by increased apical Na(+)-channel and Na-K-ATPase activity. It has been demonstrated that increases in Na-K-ATPase in response to catecholamines in the alveolar epithelium are associated with increased lung edema clearance. The cellular mechanisms involve the recruitment of new Na-K-ATPase molecules to the plasma membrane from intracellular organelles. It also appears that adenovirus-mediated Na-K-ATPase gene transfer and increased Na-K-ATPase expression may provide an alternative and efficient pathway for transient increase in alveolar fluid reabsorption and resolution of pulmonary edema.


Transcriptional profiling of human epithelial cells infected with plasmid-bearing and plasmid-deficient Chlamydia trachomatis.
Chlamydia trachomatis is an obligate intracellular epitheliotropic bacterial pathogen of humans. Infection of the eye can result in trachoma, the leading cause of preventable blindness in the world. The pathophysiology of blinding trachoma is driven by multiple episodes of reinfection of conjunctival epithelial cells, producing an intense chronic inflammatory response resulting in submucosal tissue remodeling and scarring. Recent reports have shown that infection with trachoma organisms lacking the cryptic chlamydial plasmid is highly attenuated in macaque eyes, a relevant experimental model of human trachoma infection. To better understand the molecular basis of plasmid-mediated infection attenuation and the potential modulation of host immunity, we conducted transcriptional profiling of human epithelial cells infected with C. trachomatis plasmid-bearing (A2497) and plasmid-deficient (A2497P(-)) organisms. Infection of human epithelial cells with either strain increased the expression of host genes coding for proinflammatory (granulocyte-macrophage colony-stimulating factor [GM-CSF], macrophage colony-stimulating factor [MCSF], interleukin-6 [IL-6], IL-8, IL-1α, CXCL1, CXCL2, CXCL3, intercellular adhesion molecule 1 [ICAM1]), chemoattraction (CCL20, CCL5, CXCL10), immune suppression (PD-L1, NFKB1B, TNFAIP3, CGB), apoptosis (CASP9, FAS, IL-24), and cell growth and fibrosis (EGR1 and IL-20) proteins. Statistically significant increases in the levels of expression of many of these genes were found in A2497-infected cells compared to the levels of expression in A2497P(-)-infected cells. Our findings suggest that the chlamydial plasmid plays a focal role in the host cell inflammatory response to infection and immune avoidance. These results provide new insights into the role of the chlamydial plasmid as a chlamydial virulence factor and its contributions to trachoma pathogenesis.


Decreased natural killer cytotoxic activity in chronic alcoholism is associated with alcohol liver disease but not active ethanol consumption.
Chronic alcohol intake is associated with an increased incidence of certain neoplasms. Natural killer (NK) cells have been considered to be involved in control tumor development and growth. The goal of the present study was to contribute to a better understanding of the effects of ethanol (EtOH) per se on the NK-cell population. Both patients with chronic alcoholism without liver disease (AWLD) and subjects with alcohol-induced cirrhosis (ALC) were carefully selected for this study. Immunophenotypical and functional studies of peripheral blood (PB) NK-cells were performed during active EtOH intake and after 3 months of a withdrawal period. In the AWLD group a significant increase in number of NK-cells (CD3-/CD56+) (P < .05) associated with a parallel increase in NK-cell lytic activity (P < .01) was observed. In addition, the number of cytotoxic T cells displaying the CD3+/CD56+ phenotype as well as CD8-/CD57+ NK-cell subset was also increased (P < .01 and P < .001, respectively). By contrast, in ALC patients with active EtOH intake (ALCET group), although a significant increase in the number of NK PB lymphocytes was observed (P < .05), NK lytic activity was depressed (P < .05), suggesting the existence of a decreased lytic activity/NK-cell. After 3 months of EtOH withdrawal, PB mononuclear cells (PBMC) from the AWLD group patients still displayed an increased NK cytolytic activity; in addition, the number of PB NK-cells (CD3-/CD56+ and CD8-/CD57+) and CD3+/CD56+ PB T cells continued to be increased. Independently of the duration of withdrawal period, in ALC patients EtOH withdrawal was followed by a slight decrease in the NK lytic activity of PBMC with respect to the values in active alcoholism phase; slight differences observed in the NK lytic activity in ALC patients who quit drinking could be related to the tendency to decrease of the number of NK-cells toward normal values. Furthermore, although an increase in NK cytotoxic activity after stimulation of PBMC with interleukin-2 (IL-2) was observed in ALC, it did not reach the levels observed in healthy subjects. Overall, our results show that the behavior of PB NK-cell population in chronic alcoholism is different according to both the moment of EtOH consumption and the existence or not of ALC. Alcohol by itself induced an increase in the number and lytic activity of NK-cells. By contrast, the NK cytolytic activity is constantly depressed in the stage of alcoholic cirrhosis, supporting the notion that immunosurveillance mechanisms may be affected in these patients.


Molecular characterization of the interaction of sialic acid with the periplasmic binding protein from Haemophilus ducreyi.
The primary role of bacterial periplasmic binding proteins is sequestration of essential metabolites present at a low concentration in the periplasm and making them available for active transporters that transfer these ligands into the bacterial cell. The periplasmic binding proteins (SiaPs) from the tripartite ATP-independent periplasmic (TRAP) transport system that transports mammalian host-derived sialic acids have been well studied from different pathogenic bacteria, including Haemophilus influenzae, Fusobacterium nucleatum, Pasteurella multocida, and Vibrio cholerae SiaPs bind the sialic acid N-acetylneuraminic acid (Neu5Ac) with nanomolar affinity by forming electrostatic and hydrogen-bonding interactions. Here, we report the crystal structure of a periplasmic binding protein (SatA) of the ATP-binding cassette (ABC) transport system from the pathogenic bacterium Haemophilus ducreyi The structure of Hd-SatA in the native form and sialic acid-bound forms (with Neu5Ac and N-glycolylneuraminic acid (Neu5Gc)), determined to 2.2, 1.5, and 2.5 Å resolutions, respectively, revealed a ligand-binding site that is very different from those of the SiaPs of the TRAP transport system. A structural comparison along with thermodynamic studies suggested that similar affinities are achieved in the two classes of proteins through distinct mechanisms, one enthalpically driven and the other entropically driven. In summary, our structural and thermodynamic characterization of Hd-SatA reveals that it binds sialic acids with nanomolar affinity and that this binding is an entropically driven process. This information is important for future structure-based drug design against this pathogen and related bacteria.


Chemical constituents and biological activities of Viburnum macrocephalum f. keteleeri.
Three new compounds (1-3) and seven known compounds (4-10) have been isolated from the ethanolic extract of Viburnum macrocephalum f. keteleeri using bioactivity-guided fractionation and identified as methyl (2-α-L-rhamnopyranosyloxy)acetate (1), methyl (2R-3-α-L-rhamnopyranosyloxy)glycerate (2), methyl (3R-4-α-L-rhamnopyranosyloxy-3-hydroxy)butanoate (3), bridelionoside B (4), (6S,7E,9R)-roseoside (5), linarionoside A (6), 3,7,11-trimethyl-1,6-dodecadien-3,10,11-triol (7), (+)-8-hydroxylinalool (8), β-sitosterol (9) and daucosterol (10). The structures of 1-3, including absolute configurations, were determined by spectroscopic data (1H and 13C NMR, HSQC, HMBC and ORD) and chemical methods. In addition, compounds 1-8 were assayed for their insecticidal and antimicrobial activities. Compounds 7 and 8 exhibited moderately insecticidal effects against Mythimna separata with LD50 values of 180 and 230 μg g-1, respectively. Compounds 2, 3, 7 and 8 showed varying antimicrobial activities with IC50 values ranging from 125 to 529 μM.


Helminth ova control in wastewater and sludge for advanced and conventional sanitation.
Worldwide, the most important reuse of wastewater, in volume, is agricultural irrigation. Therefore, there is a need to properly treat wastewater for such purpose, considering the removal of pathogens while leaving suitable amounts of nutrients and other compounds to increase productivity. Helminth ova are one of the main targeted pathogens in the new guidelines for water reuse in agriculture and aquaculture issued in 2006 by the World Health Organization. However, relatively little research has been done recently on how to remove and inactivate helminth ova from wastewater and sludge and recommendations given several decades ago are still used, but when put into practice, particularly in developing countries, produce unsatisfactory results. One problem is that these criteria were developed using inaccurate analytical techniques and the other is the large number and variety of helminth ova species found in wastewater and sludge from the developing world. In fact, the few technological options to remove and inactivate helminth ova come from research performed using wastewater and sludge with low helminth ova content, and refer almost only to Ascaris (one type of helminth). This paper summarises recent research work and results from practical experience concerning helminth ova control for advanced and conventional sanitation.


Colchicine May Interfere With the Efficacy of the Adenoviral Vector-Based Vaccine for COVID-19.
Under the ongoing COVID-19 pandemic, vaccines have become the crucial players to reduce the spread of the infection. Among them, the ChAdOx1 nCoV-19 vaccine is an adenoviral vector vaccine with an overall efficacy of 70.4% in protection. The engineered adenovirus contains the SARS-CoV-2 spike protein gene and pushes its DNA into the vaccinated cell's nucleus and subsequently, the spike protein can be made. During vaccination, the genome transition of adenovirus is influenced by the architecture and dynamics of the microtubule. Colchicine can alter microtubule dynamics by suppressing microtubule dynamics at lower concentrations and inducing depolymerization of microtubules at higher concentrations. Accordingly, the delivery of the genome to the vaccinated cell's nucleus by the adenoviral vector could be hindered under the presence of colchicine. Nevertheless, colchicine is a common medication for gout therapy worldwide, and though not recommended by guidelines, colchicine has even been taken into consideration as a possible therapeutic option for COVID-19 infection. Given the above reasons and the worldwide use of colchicine, the impact of colchicine on the efficacy of the COVID-19 vaccine via adenoviral vector should be viewed cautiously.


[Effects of Nrf2 on gamma-glutamylcysteine synthase in lung of guinea pigs with bronchial asthma].
To investigate the effects of Nrf2 (Nuclear-E2 related factor) on gamma-glutamylcysteine synthase (gamma-GCS) in lung of guinea pigs with bronchial asthma. 20 adult male guinea pigs were randomly divided into two groups (n = 10): control group (C group) and asthmatic group (A group), asthmatic model was established by ovalbumin intraperitoneal and ovalbumin inhalation. The reactive oxygen piece (ROS), reduced glutathione (GSH), oxidant glutathione (GSSG) and total GSH in lung tissue were examined respectively. Inflammatory cell infiltration and index of remodeling of bronchiole were detected. In situ hybridization detected the gamma-GCS heavy subunit (gamma-GCS h) mRNA in lung tissue. Immunohistochemistry detected the expression of Nrf2 protein and gamma-GCS protein in lung tissue. RT-PCR measured the expression of Nrf2 mRNA in lung tissue. The activity of gamma-GCS was measured by coupled enzyme assay. (1) The number of eosinophils and lymphocytes in bronchiole of A group were significantly higher than that of C group (P < 0.05), the remodeling of bronchiole in A group was definite. (2) ROS (U/mg pro), GSSG (micromol/g pro) and total GSH in lung tissue of A group were significantly higher than that of C group (P < 0.01). The GSH/GSSG in lung tissue of A group was much lower than that of C group (P < 0.01), GSH in lung tissue showed no difference between A group and C group. (3) Immunohistochemistry indicated that Nrf2 protein and gamma-GCS protein were more positively expressed in A group than that in C group (P < 0.01). In situ hybridization discovered that the expression of gamma-GCS-h mRNA in lung tissue of A group was more positive than that of C group. (4) RT-PCR showed that the expression of Nrf2 mRNA was no difference between A group and C group (P > 0.05). (5) The activity of gamma-GCS of A group was (28 +/- 8)U which was significantly higher than that of C group (9 +/- 2)U (P < 0.01). (6) Linear correlation analysis indicated that in lung tissue of guinea pig with asthma there existed strongly positive relationship among ROS, GSSG and the expression of Nrf2, gamma-GCS mRNA, gamma-GCS protein, the activity of gamma-GCS, there existed strongly negative relationship among GSH/GSSG and the expression of Nrf2, gamma-GCS mRNA, gamma-GCS protein, the activity of gamma-GCS. There existed oxidative stress in lung of guinea pigs with bronchial asthma, which possibly positively regulated gamma-GCS via up regulating transcription factor Nrf2.


NEUROPSYCHOLOGICAL GROUNDS IN THE AWAKE BRAIN SURGERY.
Traditionally, the awake cerebral neurosurgical interventions are carried out when the primary motor areas and the areas involved in language are concerned. This procedure is also known as mapping (Intraoperative Brain Mapping). The intraoperative neuropsychological protocol supposes the setting of a list of steps and tasks that the patient must perform during the surgery, taking into account the lesion localization (both the cortical and the subcortical structures), the cognitive functions involved and the individual particularities of each patient. As a result of the high validity of certain tests, we propose a common minimal set of tests, which can allow a minimal standardization and replicability.


Anodal transcranial direct current stimulation enhances ankle force control and modulates the beta-band activity of the sensorimotor cortex.
This study aimed to investigate the cortical responses to the ankle force control and the mechanism underlying changes in ankle force control task induced by transcranial direct current stimulation (tDCS). Sixteen young adults were recruited, and they completed the electroencephalogram (EEG) assessment and high-definition tDCS (HD-tDCS) sessions. Root mean square (RMS) error was used to evaluate ankle force control task performance. Spectral power analysis was conducted to extract the average power spectral density (PSD) in the alpha (8-13 Hz) and beta (13-30 Hz) bands for resting state and tasking (i.e. task-PSD). The ankle force control task induced significant decreases in alpha and beta PSDs in the central, left, and right primary sensorimotor cortex (SM1) and beta PSD in the central frontal as compared with the resting state. HD-tDCS significantly decreased the RMS and beta task-PSD in the central frontal and SM1. A significant association between the percent change of RMS and the percent change of beta task-PSD in the central SM1 after HD-tDCS was observed. In conclusion, ankle force control task activated a distributed cortical network mainly including the SM1. HD-tDCS applied over SM1 could enhance ankle force control and modulate the beta-band activity of the sensorimotor cortex.


Polymerase eta is a short-lived, proteasomally degraded protein that is temporarily stabilized following UV irradiation in Saccharomyces cerevisiae.
Saccharomyces cerevisiae Rad30 is the homolog of human DNA polymerase eta whose inactivation leads to the cancer-prone syndrome xeroderma pigmentosum variant. Both human and yeast polymerase eta are responsible for error-free bypass of UV-induced cis-syn pyrimidine dimers and several other DNA lesions. Here we show, using yeast strains expressing TAP-tagged Rad30, that the level of this protein is post-translationally regulated via ubiquitination and proteasome-mediated degradation. The half-life of Rad30 is 20 min and it increases due to proteasomal defects. Mutations inactivating components of the Skp1/cullin/ F-box (SCF) ubiquitin ligase complex: Skp1 and the F-box protein Ufo1 stabilize Rad30. Our results indicate also that ultraviolet irradiation causes transient stabilization of Rad30, which leads, in turn, to temporary accumulation of this polymerase in the cell. We conclude that proteolysis plays an important role in regulating the cellular abundance of Rad30. These results are the first indication of a role for controlled proteasomal degradation in modulating cellular level of translesion DNA polymerase in eukaryotes.


Diffusion Magnetic Resonance Imaging Phenotypes Predict Overall Survival Benefit From Bevacizumab or Surgery in Recurrent Glioblastoma With Large Tumor Burden.
Diffusion magnetic resonance (MR) characteristics are a predictive imaging biomarker for survival benefit in recurrent glioblastoma treated with anti-vascular endothelial growth factor (VEGF) therapy; however, its use in large volume recurrence has not been evaluated. To determine if diffusion MR characteristics can predict survival outcomes in patients with large volume recurrent glioblastoma treated with bevacizumab or repeat resection. A total of 32 patients with large volume (>20 cc or > 3.4 cm diameter) recurrent glioblastoma treated with bevacizumab and 35 patients treated with repeat surgery were included. Pretreatment tumor volume and apparent diffusion coefficient (ADC) histogram analysis were used to phenotype patients as having high (>1.24 μm2/ms) or low (<1.24 μm2/ms) ADCL, the mean value of the lower peak in a double Gaussian model of the ADC histogram within the contrast enhancing tumor. In bevacizumab and surgical cohorts, volume was correlated with overall survival (Bevacizumab: P = .009, HR = 1.02; Surgical: P = .006, HR = 0.96). ADCL was an independent predictor of survival in the bevacizumab cohort (P = .049, HR = 0.44), but not the surgical cohort (P = .273, HR = 0.67). There was a survival advantage of surgery over bevacizumab in patients with low ADCL (P = .036, HR = 0.43) but not in patients with high ADCL (P = .284, HR = 0.69). Pretreatment diffusion MR imaging is an independent predictive biomarker for overall survival in recurrent glioblastoma with a large tumor burden. Large tumors with low ADCL have a survival benefit when treated with surgical resection, whereas large tumors with high ADCL may be best managed with bevacizumab.


Comparison of hand-assisted laparoscopic surgery (HALS) and conventional laparotomy in patients with colorectal cancer: Final results from a single center.
In recent years, the use of laparoscopic surgery has been expanded to include radical curative resection. In a previous study, 212 patients with primary colorectal cancer (stages I-III) underwent radical curative resection by hand-assisted laparoscopic surgery (HALS) (n=98) or conventional laparotomy (CL) (n=114) and were compared with respect to 3-year relapse-free survival (3Y-RFS) and 3-year overall survival (3Y-OS). The study included 210/212 patients who were followed up to 5 years, including 96 patients who underwent HALS and 114 treated with CL. The two groups were matched for stage, clinical background, and postoperative management. Patient characteristics were compared and the 5Y-RFS and 5Y-OS were determined. The 5-year follow-up rate was 97.6%. In stage I-III patients, 5Y-RFS and 5Y-OS showed no significant differences between HALS and CL. The patients with stage I disease accounted for 41.7% (40/96) of the patients undergoing HALS, while stage I patients only accounted for 23.7% (27/114) of the patients undergoing CL, and the difference was significant (P=0.005). Stage II patients undergoing CL were older than those treated with HALS (P=0.017). However, there were no differences in the characteristics of stage III patients undergoing HALS or CL. In conclusion, HALS achieved a similar survival to CL in patients with stage I to III colorectal cancer. Compared with CL, HALS was performed more safely and achieved superior cosmetic results.


Herbal therapies in gastrointestinal and hepatic disorders: An evidence-based clinical review.
The gastrointestinal tract (GIT) and the liver constitute the major organs of the human body. Indeed, the very survival of the human body depends on their proper functioning. Because the GIT is a huge and complex organ system, the maintenance of proper GIT and liver health is an arduous task. GIT disturbances such as diarrhea, stomach ache, flatulence, constipation, nausea, and vomiting are very common, and they contribute to a significant burden on the healthcare system. Pharmacies are full of over-the-counter pharmacological drugs to alleviate its common conditions. However, these drugs do not always prove to be fully effective and patients have to keep on living with these ailments without a proper and long-term solution. The aim of this review article is to present a practical reference guide to the role of herbal medicines in dealing with gastrointestinal and hepatic disorders, which is supported by systematic reviews and evidence-based trials. People have depended on herbal medications for centuries for the treatment of various ailments of the GIT, liver, and other organ system problems. Recently, this trend of incorporating herbal medication for the treatment of various diseases in both developing and developed countries have surged. Many people continue to use herbal medications, even though substantial data about their efficacy, uses, and toxicological effects do not exist. In addition, while herbal medicines have enormous benefits in both the prevention and the treatment of medical ailments, they can also have toxicological effects. It is, therefore, of the utmost importance that appropriate time, energy, and resources are spent on the development of ethnopharmacology. In addition, herbal products should be classified in a pattern similar to pharmacological medications, including their uses, side effects, mechanism of action, efficacy, and so on.


[Fifty years history of new drugs in Japan: the developments and trends of antihypertensive drugs].
The novel antihypertensive drugs which have been discovered and developed in the latter half of the 20th century were investigated. Newly discovered or improved drugs are approved by the Ministry of Health and Welfare in Japan, and after then they become available for clinical use. We can follow the progress and trends of various new antihypertensive drugs by recording their years of approval. The four primary useful drugs for the treatment of hypertension were developed were introduced as listed in the following: 1. Antihypertensive diuretics: Thiazide and dihydrothiazide were first approved in 1958, and various related drugs including aldosterone antagonists and loop diuretics followed. 2. beta-Adrenergic-blocking drugs: Propranolol was approved in 1966 for heart diseases and for hypertension in 1970. Thereafter many related drugs were developed. 3. Calcium channel-blocking drugs: Nifedipine was approved, for heart disease in 1974 and for hypertension in 1981, and then many related drugs appeared. 4. Angiotensin-converting enzyme inhibitors: Captopril was approved in 1982 and thereafter various related drugs followed. The four categories of these drugs were selected as first choice drugs for the treatment of hypertension in 1988. The development of these excellent useful drugs affected the mortality rates of cerebrovascular diseases (e.g., apoplexy). The mortality curve reaches plateaued in 1963, peaked in 1965, and then declined rapidly. Antihypertensive diuretic drugs stop the rise of mortality, and beta-blocking drugs, Ca-antagonists and ACE-inhibitors promote rapid downward tendency.


Left ventricular performance in diabetic patients without clinical heart disease. Evaluation by systolic time intervals and echocardiography.
To examine left ventricular performance in diabetic patients without clinical evidence of cardiac involvement, systolic time intervals (pre-ejection period, left ventricular ejection time index and ratio of pre-ejection period to left ventricular ejection time) and echocardiographic measures (percentage changes in minor axis diameter, end-diastolic and end-systolic diameter, end- diastolic volume and end-systolic volumes, stroke volume and ejection fraction), were obtained. There were 89 diabetic patients and 93 control subjects evaluated for systolic time intervals, and 40 diabetic patients and 20 control subjects evaluated by echocardiogram. The diabetic group demonstrated significant (P less than 0.001) differences from the normal control group in each of the noninvasive measures of systolic time intervals. Pre-ejection period/left ventricular ejection time ration was increased by 25 percent and the pre-ejection period was increased by 12 percent in the diabetic patients. Among 40 diabetic patients studied by echocardiography, abnormal percentage change in minor axis diameter, (less than 30 percent) occurred in six individuals. Ejection fraction was decreased by 20 percent as compared to the control group, whereas end-diastolic pressure was not significantly different in the groups.


Health care providers' training, perceptions, and practices regarding stress and health outcomes.
In order to assess health care providers' training, perceptions, and practices regarding stress and health outcomes, a survey was administered to primary care providers in the outpatient medical clinics of a southeastern urban hospital serving a predominantly African-American indigent population. One-hundred-fifty-one of 210 providers (72%) responded. Forty-two percent of respondents reported receiving no instruction regarding stress and health outcomes during their medical/professional education. While 90% believed stress management was "very" or "somewhat" effective in improving health outcomes, 45% "rarely" or "never" discussed stress management with their patients. Respondents were twice as likely to believe that counseling patients about smoking, nutrition, or exercise was more important than counseling them about stress. Seventy-six percent lacked confidence in their ability to counsel patients about stress. The majority of respondents (57%) "rarely" or "never" practiced stress reduction techniques themselves. Belief in the importance of stress counseling, its effectiveness in improving health, and confidence in one's ability to teach relaxation techniques were all related to the probability that providers would counsel patients regarding stress. There is a need for curriculum reform that emphasizes new knowledge about stress and disease, new skills in stress reduction, and more positive beliefs about mind/body medicine and its integration into the existing health care structure.


Lymphocyte subsets of maxillary mucosa in chronic inflammation.
Subsets of infiltrating lymphocytes within maxillary sinus mucosae of patients with chronic sinusitis were investigated by immunoperoxidase staining of frozen sections with the use of monoclonal antibodies. The most commonly observed infiltrating cell type was suppressor/cytotoxic T cells (CD8+) and smaller subpopulations of lymphocytes were helper/inducer T cells (CD4+) and B cells (CD20+). Variable numbers of HLA-DR+ cells were commonly observed in the lamina propria. The fibrous type of chronic sinusitis was found to have more suppressor/cytotoxic T cells (CD8+) and lower CD4/CD8 ratio than the other histopathological types.


Clinical dose-regimen studies with latanoprost, a new ocular hypotensive PGF2 alpha analogue.
This review summarizes recent short-term clinical studies evaluating the ocular hypotensive efficacy of different dose-regimens of latanoprost. When tested in ocular hypertensive and glaucoma patients concomitantly treated with timolol, 0.006% latanoprost given only in the evening, was found to be more effective than the same concentration given in the morning and evening. In patients with open angle, pseudoexfoliation and normal tension glaucoma not receiving other treatment, once-daily 0.005% latanoprost monotherapy was more effective than twice-daily 0.0015% latanoprost treatment. No significant differences were found in conjunctival hyperemia, sensory irritation or blood-aqueous barrier permeability between these two treatment regimens. Although the ocular hypotensive efficacy of once-daily application of the lower concentration (0.0015%) latanoprost was not investigated, we would conclude, based on the studies reviewed here, that at a concentration of 0.005%, once-a-day dosing of latanoprost is highly effective in significantly reducing intraocular pressure, causing only minimal, clinically acceptable short-term ocular side effects.


"Souvenir" casting silicosis.
A case of silicosis in a 47-year-old worker who was employed for many years in a small souvenir casting shop is described. This work site demonstrates many unfavorable characteristics of small industries, such as lack of awareness of the need for safety measures, exposure control, protection of workers, and lack of compliance with environmental and medical-legal standards.


[Expression and correlation of Skp2 and p27(kip1) in 92 cases of non-Hodgkin's lymphoma].
To investigate the expression and correlation of Skp2 and p27kipl in non-Hodgkin's lymphoma. The expression of Skp2, p27(kip1) and Ki-67 (the proliferation index)were detected in sections of 92 cases of non-Hodgkin's lymphoma (NHL) and 14 cases of reactive lymph nodes by immunohistochemistry and histopathology. The expression of Skp2 and p27(kip1) in 4 NHL cell lines were detected by Western blot. The expression of Skp2 in NHL cases were significantly higher than that in reactive lymph nodes (except the germinal centers), positively correlated with proliferation activity, and an increasing tumor aggressiveness was associated with the increased expression of Skp2. The expression of p27(kip1) protein in NHL cases were significantly lower than that in reactive lymph nodes (except the germinal centers), negatively correlated with proliferation activity, and an increasing tumor aggressiveness was associated with decreased expression of p27(kip1). The statistical analysis indicated that there was no obvious correlation between Skp2 and p27(kip1) expression in NHL tissues. The higher expression of Skp2 and lower expression of p27(kip1) in NHL tissues may play a role in the tumorigenesis and development of NHL.


[Impact and clinical value of the revised 2019 Chinese HER-2 testing guidelines on the detect result evaluation of invasive breast cancer cases with equivocal HER-2 immunostaining by using fluorescence in situ hybridization].
Objective: To investigate the impact and clinical significance of the revised 2019 Chinese HER-2 testing guidelines on the detecting result evaluation of invasive breast cancers with equivocal HER-2 immunostaining by using fluorescence in situ hybridization (FISH). Methods: A total of 569 cases of invasive breast cancers with HER-2 (+ + ) immunostaining evaluated according to the immunohistochemistry (IHC) guidelines of 2014 edition and 2019 edition from May to November 2019 were collected and further detected by FISH. The results of HER-2/CEPl7 double probe were respectively interpreted according to both the 2014 and 2019 Chinese HER-2 testing guidelines and the results were compared. Results: According to the 2014 guidelines, the number of HER-2 positive, equivocal and negative cases were 139 (24.43%), 67 (11.78%), and 363 (63.80%), respectively. Whereas according to the 2019 guidelines, 115 cases (20.21%) were the first group, 9 cases (1.58%) were the second group, 15 cases (2.64%) were the third group, 67 cases (11.78%) were the fourth group, and 363 cases were (63.80%) the fifth group, of which 130 cases (22.85%) were positive and 439 cases (77.15%) were negative by FISH detecting. Compared with the guideline of 2014 edition, the HER-2 positive rate of FISH detection reduced from 24.43% (139/569) to 22.85% (130/559) according to the application of the guideline of 2019 edition, but the difference was not statistically significant (P=0.567), while the negative rate increased from 63.80% (363/569) to 77.15% (439/569), with a statistically significant difference (P<0.05). Forty-three cases with incomplete weak to medium intensity of IHC membrane staining which were HER-2 (+ + ) according to 2014 guideline were changed to IHC (+ ) on the basis of the 2019 guideline. According to the FISH guideline of 2014 edition, 1 case (2.33%) was positive, 6 cases (13.95%) was equivocal and 36 cases (83.72%) was negative, while according to the 2019 FISH guideline, all of the 43 cases were negative. Conclusions: According to the guideline of 2019 edition, a proportion of cases changes from HER-2 (+ + ) to (+ ), and the HER-2 positive rate of FISH test decreases slightly, the negative rate increases, the equivocal result is eliminated, which provides a definite reference for screening patients who will be benefited from the targeted treatment of HER-2.


Algorithmic strategies for the single nucleotide polymorphism haplotype assembly problem.
With the consensus human genome sequenced and many other sequencing projects at varying stages of completion, greater attention is being paid to the genetic differences among individuals and the abilities of those differences to predict phenotypes. A significant obstacle to such work is the difficulty and expense of determining haplotypes--sets of variants genetically linked because of their proximity on the genome--for large numbers of individuals for use in association studies. This paper presents some algorithmic considerations in a new approach for haplotype determination: inferring haplotypes from localised polymorphism data gathered from short genome 'fragments.' Formalised models of the biological system under consideration are examined, given a variety of assumptions about the goal of the problem and the character of optimal solutions. Some theoretical results and algorithms for handling haplotype assembly given the different models are then sketched. The primary conclusion is that some important simplified variants of the problem yield tractable problems while more general variants tend to be intractable in the worst case.


Joint spectral intensity of entangled photon pairs from a warm atomic ensemble via stimulated emission beat interferometry.
Photonic quantum states generated from atomic systems play prominent roles in long-distance quantum networks and scalable quantum communication, because entangled photon pairs from atomic ensembles possess a universal identity and narrow spectral bandwidth for quantum repeaters. In this study, we propose and demonstrate a novel, to the best of our knowledge, method for the joint spectral intensity measurement of narrowband continuous wave (CW)-mode photon pairs from a warm atomic ensemble using stimulated emission and beat interferometry for the first time. Our approach offers the advantage of sub-megahertz resolution, absolute optical frequency measurements with megahertz-level accuracy, fast collection time, and high signal-to-noise ratio; thus, our method can find important applications in the characterization of narrowband photon pairs generated from sources including atoms and artificially structured material.


Downregulation of genes related to immune and inflammatory response in IVF implantation failure cases under controlled ovarian stimulation.
Implantation failure (IF) even after the good-quality embryo transfer (ET) is main obstacle in in vitro fertilization (IVF). We aim to study the genomics of endometrial receptivity in IF patients under controlled ovarian stimulation (COS) during which ET is generally practised in IVF. Endometrial gene expression profiling in IF patients (n=10) and oocyte donors (n=8) were compared during window of implantation under COS by microarray. Enrichment analysis of microarray data was performed to determine dysregulated pathways. Microarray results were validated by real-time PCR. Localization of genes related to immune response (progestagen-associated endometrial protein (PAEP), leukaemia inhibitory factor (LIF), interleukin-6 signal transducer (IL6ST) was detected by immunohistochemistry. The gene ontology, pathway analysis and enrichment mapping revealed significant downregulation in activation and regulation of immune and inflammation response in IF patients under COS. The lower expression of PAEP, LIF and IL6ST in cases compared to controls by real time and immunohistochemistry suggests the functional importance of these genes. Importance of immune and inflammatory response in endometrial receptivity adds on to the current knowledge of gene expression profile in IF under COS. The panel of genes involved in these pathways would be useful in determining further line of treatment for IF during IVF.


[Inhibitory effect of polydatin on expression of toll-like receptor 4 in ischemia-reperfusion injured NRK-52E cells].
Polydatin is a monocrystaline compound isolated from Polygonum cuspidatum Sieb. et Zucc. (Polygonaceae) with biological properties, such as anti-inflammation, anti-oxidative and nephroprotective effects. Increasing number of studies have demonstrated the protective effect of polydatin on renal ischemia reperfusion injury. However, the possible mechanisms of this protection are not fully elucidated. This study aimed to investigate the effect of polydatin on ischemia-reperfusion induced expression of toll-like receptor4 (TLR4) in rat renal tubular epithelia cells (NRK-52E), and analyze the mechanism of polydatin on TLR4 signal pathway. The cultured NRK-52E cells were incubated in three gas incubators for a period of 6 h at hypoxia and 24h at reoxygenation to simulate the ischemia-reperfusion injury in vitro. TLR4 mRNA level was analyzed by real-time-PCR, and the protein expression of TLR4 and NF-κB by Western blotting, while TNF-α and IL-1β proteins expressions were detected by ELISA. Polydatin downregulated I/R induced mRNA and protein expressions of TLR4, and decreased the protein expression of NF-κB, TNF-α and IL-1β. The TLR4 blocker partially antagonized the effect of I/R on NF-κB signaling, and such inhibitory effect was markedly enhanced by polydatin. In the present study, polydatin protects NRK-52E cells from I/R injury possibly by relieving the inflammatory response through regulation of TLR4/NF-κB signaling pathway.


Caffeic acid and hydroxytyrosol have anti-obesogenic properties in zebrafish and rainbow trout models.
Some natural products, known sources of bioactive compounds with a wide range of properties, may have therapeutic values in human health and diseases, as well as agronomic applications. The effect of three compounds of plant origin with well-known dietary antioxidant properties, astaxanthin (ATX), caffeic acid (CA) and hydroxytyrosol (HT), on zebrafish (Danio rerio) larval adiposity and rainbow trout (Onchorynchus mykiss) adipocytes was assessed. The zebrafish obesogenic test (ZOT) demonstrated the anti-obesogenic activity of CA and HT. These compounds were able to counteract the obesogenic effect produced by the peroxisome proliferator-activated receptor gamma (PPARγ) agonist, rosiglitazone (RGZ). CA and HT suppressed RGZ-increased PPARγ protein expression and lipid accumulation in primary-cultured rainbow trout adipocytes. HT also significantly reduced plasma triacylglycerol concentrations, as well as mRNA levels of the fasn adipogenic gene in the adipose tissue of HT-injected rainbow trout. In conclusion, in vitro and in vivo approaches demonstrated the anti-obesogenic potential of CA and HT on teleost fish models that may be relevant for studying their molecular mode of action. Further studies are required to evaluate the effect of these bioactive components as food supplements for modulating adiposity in farmed fish.


Mechanisms of regulation of urease biosynthesis in Proteus rettgeri.
Urease of Proteus rettgeri is an inducible enzyme synthesized specifically in the presence of urea; urea analogues did not act as inducers. Once initiated, the biosynthesis of the enzyme proceeded as a constant fraction of the total protein formed. The rate of urease formation was affected by the carbon source used. In comparison with glycerol, glucose inhibited enzyme synthesis. The addition of ammonium ions to the inducing medium also decreased the rate of urease biosynthesis, and when ammonium ions were present urease activity and urea transport across the cell membrane were inhibited. A kinetic analysis of urease inhibition by ammonium ions, by use of a partially purified preparation of urease, showed that it was a competitive inhibition.