Ligation of ICAM-1 on endothelial cells leads to expression of VCAM-1 via a nuclear factor-kappaB-independent mechanism.
ICAM-1 is an Ig-like cell adhesion molecule expressed by several cell types, including the endothelium. Cross-linking of ICAM-1 on the surface of different cell types has previously been shown to cause an increase in cellular activation within the cytoplasm. In this study, we have compared signaling events following ligation of ICAM-1 by cross-linking with mAbs with events after activation of HUVEC by TNF. ICAM-1 cross-linking caused activation of Erk-1 and the AP-1 transcription factor complex, without any increase in NF-kappaB activity, in contrast to TNF stimulation. Transcription of VCAM-1 mRNA was observed by reverse-transcriptase PCR after ICAM-1 cross-linking, with no associated transcription of E-selectin. This was reflected by the presence of VCAM-1 protein after immunoprecipitation, without E-selectin expression, in ICAM-1 cross-linked cells. In contrast, mRNA and protein for both VCAM-1 and E-selectin were observed in TNF-treated HUVEC, as expected. Addition of the MEK (MAP/Erk kinase) inhibitor PD98059 reduced expression of VCAM-1 after ICAM-1 cross-linking, suggesting that the Erk pathway is involved in ICAM-1-mediated VCAM-1 expression. In conclusion, ICAM-1-induced expression of VCAM-1 represents a pathway for adhesion molecule up-regulation that is distinct from the TNF-induced pathway. It may be similar to the IL-4 pathway or it may represent a novel pathway.


Characterization of the catalytic activity of the membrane-anchored metalloproteinase ADAM15 in cell-based assays.
ADAM15 (a disintegrin and metalloproteinase 15) is a membrane-anchored metalloproteinase, which is overexpressed in several human cancers and has been implicated in pathological neovascularization and prostate cancer metastasis. Yet, little is known about the catalytic properties of ADAM15. Here, we purified soluble recombinant ADAM15 to test for its ability to cleave a library of peptide substrates. However, we found no processing of any of the peptide substrates tested here, and therefore turned to cell-based assays to characterize the catalytic properties of ADAM15. Overexpression of full-length membrane-anchored ADAM15 or the catalytically inactive ADAM15E-->A together with various membrane proteins resulted in increased release of the extracellular domain of the fibroblast growth factor receptor 2iiib (FGFR2iiib) by ADAM15, but not ADAM15E-->A. This provided a robust assay for a characterization of the catalytic properties of ADAM15 in intact cells. We found that increased expression of ADAM15 resulted in increased FGFR2iiib shedding, but that ADAM15 was not stimulated by phorbol esters or calcium ionophores, two commonly used activators of ectodomain shedding. Moreover, ADAM15-dependent processing of FGFR2iiib was inhibited by the hydroxamate-based metalloproteinase inhibitors marimastat, TAPI-2 and GM6001, and by 50 nM TIMP-3 (tissue inhibitor of metalloproteinases 3), but not by 100 nM TIMP-1, and only weakly by 100 nM TIMP-2. These results define key catalytic properties of ADAM15 in cells and its response to stimulators and inhibitors of ectodomain shedding. A cell-based assay for the catalytic activity of ADAM15 could aid in identifying compounds, which could be used to block the function of ADAM15 in pathological neovascularization and cancer.


Numerical solution of the stationary multicomponent nonlinear Schrödinger equation with a constraint on the angular momentum.
We formulate a damped oscillating particle method to solve the stationary nonlinear Schrödinger equation (NLSE). The ground-state solutions are found by a converging damped oscillating evolution equation that can be discretized with symplectic numerical techniques. The method is demonstrated for three different cases: for the single-component NLSE with an attractive self-interaction, for the single-component NLSE with a repulsive self-interaction and a constraint on the angular momentum, and for the two-component NLSE with a constraint on the total angular momentum. We reproduce the so-called yrast curve for the single-component case, described in [A. D. Jackson et al., Europhys. Lett. 95, 30002 (2011)], and produce for the first time an analogous curve for the two-component NLSE. The numerical results are compared with analytic solutions and competing numerical methods. Our method is well suited to handle a large class of equations and can easily be adapted to further constraints and components.


Simultaneous gene transfer of bone morphogenetic protein (BMP) -2 and BMP-7 by in vivo electroporation induces rapid bone formation and BMP-4 expression.
Transcutaneous in vivo electroporation is expected to be an effective gene-transfer method for promoting bone regeneration using the BMP-2 plasmid vector. To promote enhanced osteoinduction using this method, we simultaneously transferred cDNAs for BMP-2 and BMP-7, as inserts in the non-viral vector pCAGGS. First, an in vitro study was carried out to confirm the expression of BMP-2 and BMP-7 following the double-gene transfer. Next, the individual BMP-2 and BMP-7 plasmids or both together were injected into rat calf muscles, and transcutaneous electroporation was applied 8 times at 100 V, 50 msec. In the culture system, the simultaneous transfer of the BMP-2 and BMP-7 genes led to a much higher ALP activity in C2C12 cells than did the transfer of either gene alone. In vivo, ten days after the treatment, soft X-ray analysis showed that muscles that received both pCAGGS-BMP-2 and pCAGGS-BMP-7 had better-defined opacities than those receiving a single gene. Histological examination showed advanced ossification in calf muscles that received the double-gene transfer. BMP-4 mRNA was also expressed, and RT-PCR showed that its level increased for 3 days in a time-dependent manner in the double-gene transfer group. Immunohistochemistry confirmed that BMP-4-expressing cells resided in the matrix between muscle fibers. The simultaneous transfer of BMP-2 and BMP-7 genes using in vivo electroporation induces more rapid bone formation than the transfer of either gene alone, and the increased expression of endogenous BMP-4 suggests that the rapid ossification is related to the induction of BMP-4.


Resistance of surface coating resins against toothbrushing abrasion.
To evaluate the durability of a resin coating system after toothbrushing abrasion resistance and surface hardness of the coating resin. Rectangular blocks of Top Coat (TC) or the bonding resin of the two-step self-etching adhesive Clearfil SE Bond (SEB) were prepared by irradiation with halogen light units. After immersion in distilled water at 37 degrees C until stabilized water absorption, the specimens were subjected to toothbrushing abrasion tests in which a toothbrush was moved on the specimen at 60 strokes/minute with a 400 gf vertical load with toothpaste slurry. The specimens were weighed after every 10,000 strokes until 200,000 strokes. Hardness of the specimen was measured with a Knoop hardness tester, and the degree of cure was determined using ATR-FTIR spectroscopy. Statistical differences between materials were analyzed using a Student's t-test. TC demonstrated significantly less weight loss than SEB after 40,000 strokes (P<0.05), showing 0.87 +/- 0.64 mg loss after 200,000 strokes. The Knoop hardness number of TC was significantly greater than that of SEB (P<0.05), and TC presented a greater degree of cure.


Gene therapy for PRPH2-associated ocular disease: challenges and prospects.
The peripherin-2 (PRPH2) gene encodes a photoreceptor-specific tetraspanin protein called peripherin-2/retinal degeneration slow (RDS), which is critical for the formation and maintenance of rod and cone outer segments. Over 90 different disease-causing mutations in PRPH2 have been identified, which cause a variety of forms of retinitis pigmentosa and macular degeneration. Given the disease burden associated with PRPH2 mutations, the gene has long been a focus for preclinical gene therapy studies. Adeno-associated viruses and compacted DNA nanoparticles carrying PRPH2 have been successfully used to mediate improvement in the rds(-/-) and rds(+/-) mouse models. However, complexities in the pathogenic mechanism for PRPH2-associated macular disease coupled with the need for a precise dose of peripherin-2 to combat a severe haploinsufficiency phenotype have delayed the development of clinically viable genetic treatments. Here we discuss the progress and prospects for PRPH2-associated gene therapy.


Breaking the ESG rating divergence: An open geospatial framework for environmental scores.
Information about a company's environmental, social and governance (ESG) performance has become increasingly important in the decision-making process of financial institutions. The financial implications of environmental challenges (e.g. water stress), negative social impacts (e.g. health impacts in local communities) or poor corporate governance (e.g. breaching legislation) all continue to increase. Accordingly, there is a need for financial institutions to incorporate information on ESG risks, opportunities and impacts in decisions that relate to risk management, investments, credit, strategy, and reporting. ESG information is typically disseminated through ESG ratings, which combine the three constituents into a single rating, or ascribe them separate scores. The compilation of ESG ratings and the identification of appropriate data sources is an inherently complex process; as such, there is no single standard for data collection or reporting. This has led to a divergence in the underlying data sources used by different rating providers, as well as in the determination of factors that are deemed worthy of measurement in the first place. For example, when assessing a company's environmental impact, one rating provider may rely on company-provided data, while another may incorporate independent third-party assessments. Unfortunately, there is currently no clear mechanism for effectively resolving such disagreements to establish a standardised approach to ESG rating assessments. However, geospatial data and analyses offer several key advantages for ESG assessments, including consistency, the potential for enhanced accuracy, and the ability to identify and assess environmental impacts at a detailed physical asset level, in addition to evaluating the broader spatial context. By incorporating geospatial information (obtained through manually processing remotely sensed data, or by using existing products) rating methodologies can be improved, and disparities can be addressed more effectively. This would enable a more comprehensive understanding of the environmental considerations of ESG assessments, promoting a more informed and precise decision-making process. Within this context, a few institutions (e.g. the University of Oxford, the WWF, and a few others) are pioneering thought leadership around spatial finance, including the assessment of ESG issues utilising geospatial intelligence, but there are no consistent frameworks for incorporating geospatial data into ESG ratings and analysis. This paper explores the opportunity for such a geospatial environmental scoring framework, defining a variety of methods in which open data with broad geographic coverage could be incorporated into ESG analysis, generalisable to a range of assets and sectors. The proposed framework is organised into two categories: localised effects, which directly impact the immediate vicinity of an asset, and delocalised effects, which contribute to global climate change and atmospheric pollution. Sub-scores are defined within these categories, which capture both the localised effects on land use, biodiversity, soils, and hydrology, and the global impacts resulting from atmospheric emissions. The approaches for handling geospatial data to generate both these sub-scores and the final E-score are presented, including a test case, and the complete methodology is made available in open repositories.


[Free amino acid content in the blood and urine from the use of monomycin on children with dysentery].
The progress of acute dysentery in 73 children at the age of 1 to 14 years treated with monomycin and the levels of free amino acids in the blood and urine in dynamics were studied. It was found that the blood levels of 6 amino acids in the children treated with the antibiotics significantly decreased, while those of 3 amino acids increased as compared to the levels of the same amino acids in the children treated without the antibiotics. It was concluded that the diet of dysentery children treated with monomycin should contain stimulators of protein synthesis and increased amounts of protein.


Targeting of the MYCN protein with small molecule c-MYC inhibitors.
Members of the MYC family are the most frequently deregulated oncogenes in human cancer and are often correlated with aggressive disease and/or poorly differentiated tumors. Since patients with MYCN-amplified neuroblastoma have a poor prognosis, targeting MYCN using small molecule inhibitors could represent a promising therapeutic approach. We have previously demonstrated that the small molecule 10058-F4, known to bind to the c-MYC bHLHZip dimerization domain and inhibiting the c-MYC/MAX interaction, also interferes with the MYCN/MAX dimerization in vitro and imparts anti-tumorigenic effects in neuroblastoma tumor models with MYCN overexpression. Our previous work also revealed that MYCN-inhibition leads to mitochondrial dysfunction resulting in accumulation of lipid droplets in neuroblastoma cells. To expand our understanding of how small molecules interfere with MYCN, we have now analyzed the direct binding of 10058-F4, as well as three of its analogs; #474, #764 and 10058-F4(7RH), one metabolite C-m/z 232, and a structurally unrelated c-MYC inhibitor 10074-G5, to the bHLHZip domain of MYCN. We also assessed their ability to induce apoptosis, neurite outgrowth and lipid accumulation in neuroblastoma cells. Interestingly, all c-MYC binding molecules tested also bind MYCN as assayed by surface plasmon resonance. Using a proximity ligation assay, we found reduced interaction between MYCN and MAX after treatment with all molecules except for the 10058-F4 metabolite C-m/z 232 and the non-binder 10058-F4(7RH). Importantly, 10074-G5 and 10058-F4 were the most efficient in inducing neuronal differentiation and lipid accumulation in MYCN-amplified neuroblastoma cells. Together our data demonstrate MYCN-binding properties for a selection of small molecules, and provide functional information that could be of importance for future development of targeted therapies against MYCN-amplified neuroblastoma.


Comparison of the ocular surface changes following the use of two different prostaglandin F2α analogues containing benzalkonium chloride or polyquad in rabbit eyes.
The aim of this study is to compare the effect of prostaglandin analogues preserved with either 0.015% or 0.001% benzalkoium chloride (BAK); or 0.001% polyquad (PQ) on the ocular surface of rabbit eyes. Forty white rabbits were randomized to receive four-times daily instillation of either 0.0015% tafluprost (TF) preserved with 0.001% BAK (TF-BAK); 0.004% travoprost (TR) with 0.015% BAK (TR-BAK) or 0.001% PQ (TR-PQ); or preservative-free artificial tears in one eye for a 4-week period. Tear samples collected from the 40 rabbits were analyzed by enzyme-linked immunosorbent assays (ELISA) to identify the presence of inflammatory cytokines: interleukin (IL)-1β and IL-6 on day 14. Subsequently, harvested cornea and bulbar conjunctiva were evaluated using light and transmission electron microscopy (TEM). IL-6 was significantly increased in TF-BAK and TR-BAK groups compared to controls and TR-PQ group (p = 0.005); however, IL-1β level was not significantly different among four groups (p = 0.360). Rabbits treated with TR-BAK showed decreased goblet cell density of bulbar conjunctiva and increased pyknotic change and vacuolization of corneal epithelial cells on light microscopy; similar change occurred but was less severe in TF-BAK group. The TR-PQ group showed similar results as the controls. The destruction of the microvillar architecture of bulbar conjunctiva and cornea was most prominent in the TR-BAK group. Preservatives included in the anti-glaucoma eye-drops showed different ocular surface changes according to the concentration and type in the rabbits. Prostaglandin analogues preserved with higher level of BAK may cause more harmful effects on the ocular surface than PQ-preserved medications.


Definitive care for the critically ill during a disaster: a framework for optimizing critical care surge capacity: from a Task Force for Mass Critical Care summit meeting, January 26-27, 2007, Chicago, IL.
Plausible disasters may yield hundreds or thousands of critically ill victims. However, most countries, including those with widely available critical care services, lack sufficient specialized staff, medical equipment, and ICU space to provide timely, usual critical care for a large influx of additional patients. Shifting critical care disaster preparedness efforts to augment limited, essential critical care (emergency mass critical care [EMCC]), rather than to marginally increase unrestricted, individual-focused critical care may provide many additional people with access to life-sustaining interventions. In 2007, in response to the increasing concern over a severe influenza pandemic, the Task Force on Mass Critical Care (hereafter called the Task Force) convened to suggest the essential critical care therapeutics and interventions for EMCC. EMCC should include the following: (1) mechanical ventilation, (2) IV fluid resuscitation, (3) vasopressor administration, (4) medication administration for specific disease states (eg, antimicrobials and antidotes), (5) sedation and analgesia, and (6) select practices to reduce adverse consequences of critical illness and critical care delivery. Also, all hospitals with ICUs should prepare to deliver EMCC for a daily critical care census at three times their usual ICU capacity for up to 10 days. By using the Task Force suggestions for EMCC, communities may better prepare to deliver augmented critical care in response to disasters. In light of current mass critical care data limitations, the Task Force suggestions were developed to guide preparedness but are not intended as strict policy mandates. Additional research is required to evaluate EMCC and revise the strategy as warranted.


HGF/MET in osteogenic differentiation of primary human palatal periosteum-derived mesenchymal stem cells.
This study aimed to determine expressions of hepatocyte growth factor (HGF) and MET proto-oncogene receptor tyrosine kinase (MET) in palatal periosteum (PP) and to examine the effect of HGF/MET on osteogenic differentiation of human palatal periosteum-derived mesenchymal stem cells (PD-MSCs). HGF/MET proteins in human palatal periosteum (n = 3) were localized using immunohistochemistry. PD-MSCs (n = 3) were cultured in serum-free Essential 8 (E8) medium or osteogenic medium with and without Capmatinib, a selective ATP-inhibitor of MET. HGF concentration in vitro was measured with ELISA. Relative gene expression was quantified from PD-MSCs by quantitative reverse transcription real-time polymerase chain reaction. Immunohistochemistry detected co-localization of HGF and MET protein in PP. HGF protein levels were significantly higher (P < 0.05) in osteogenic media (day 21: 12.19 ± 8.36 ng/mL) than in E8 medium (day 21: 0.42 ± 0.72 ng/mL). MET inhibitor had a limited feedback effect on the expression profile of the osteogenic genes tested. Gene expression levels for all but three genes were comparable in serum-free and osteogenic media at all time points. HGF/MET present in human PP and HGF is upregulated in vitro during osteogenesis; however the targeted pathways controlled by MET may not involve osteoblast maturation.


Laboratory findings in cows after experimental infection with Ehrlichia phagocytophila.
The goal of this study was to assess various hematological variables in 10 cows after experimental infection with Ehrlichia phagocytophila. Blood samples were collected at regular intervals for examination of leukocytes for Ehrlichia organisms and for determination of hematological and biochemical variables. In addition, PCR amplification was performed throughout the disease period on blood and milk samples for the detection of E. phagocytophila organisms. The time of seroconversion and the duration of serum titers indicating positivity were determined by indirect immunofluorescence. For all cows, E. phagocytophila organisms were first detected microscopically in leukocytes 5 to 8 days postinfection and could be demonstrated for a period of 6 to 14 days. For all cows, the appearance of E. phagocytophila organisms in leukocytes coincided with transient erythropenia, leukopenia, and thrombocytopenia and a decrease in hematocrit and hemoglobin concentration. For five lactating cows, E. phagocytophila organisms were identified in leukocytes of milk samples during the acute phase of the disease, which, we believe, has not previously been reported. E. phagocytophila DNA was detected in blood samples by nested PCR from 1 to 2 days before to 2 to 12 days after the organisms were identified microscopically. In milk samples, E. phagocytophila DNA was detected for an average of 11 days.


Therapeutic effects of curcumin on sepsis and mechanisms of action: A systematic review of preclinical studies.
Sepsis is a complex disease that begins with an infectious disorder and causes excessive immune responses. Curcumin is considered as an active component of turmeric that can improve the condition in sepsis due to its anti-inflammatory and antioxidant properties. PubMed, Embase, Google Scholar, Web of Science, and Scopus databases were searched. Searching was not limited to a specific publication period. Only English-language original articles, which had examined the effect of curcumin on sepsis, were included. At first, 1,098 articles were totally found, and 209 articles were selected after excluding duplicated data; 46 articles were remained due to the curcumin effects on sepsis. These included 23 in vitro studies and 23 animal studies. Our results showed that curcumin and various analogs of curcumin can have an inhibitory effect on sepsis-induced complications. Curcumin has the ability to inhibit the inflammatory, oxidative coagulation factors, and regulation of immune responses in sepsis. Despite the promising evidence of the therapeutic effects of curcumin on the sepsis complication, further studies seem necessary to investigate its effect and possible mechanisms of action in human studies.


All-polymer organic semiconductor laser chips: parallel fabrication and encapsulation.
Organic semiconductor lasers are of particular interest as tunable visible laser light sources. For bringing those to market encapsulation is needed to ensure practicable lifetimes. Additionally, fabrication technologies suitable for mass production must be used. We introduce all-polymer chips comprising encapsulated distributed feedback organic semiconductor lasers. Several chips are fabricated in parallel by thermal nanoimprint of the feedback grating on 4″ wafer scale out of poly(methyl methacrylate) (PMMA) and cyclic olefin copolymer (COC). The lasers consisting of the organic semiconductor tris(8-hydroxyquinoline) aluminum (Alq3) doped with the laser dye 4-dicyanomethylene-2-methyl-6-(p-dimethylaminostyril)-4H-pyrane (DCM) are hermetically sealed by thermally bonding a polymer lid. The organic thin film is placed in a basin within the substrate and is not in direct contact to the lid. Thus, the spectral properties of the lasers are unmodified in comparison to unencapsulated lasers. Grating periods of 378 nm to 428 nm in steps of 10 nm result in lasing at wavelengths of 622 nm to 685 nm. The operational lifetime of the lasers expressed in number of pulses is improved 11-fold (PMMA) and 3-fold (COC) in comparison to unencapsulated PMMA devices.


Mathematical modelling of earlier stages of COVID-19 transmission dynamics in Ghana.
In late 2019, a novel coronavirus, the SARS-CoV-2 outbreak was identified in Wuhan, China and later spread to every corner of the globe. Whilst the number of infection-induced deaths in Ghana, West Africa are minimal when compared with the rest of the world, the impact on the local health service is still significant. Compartmental models are a useful framework for investigating transmission of diseases in societies. To understand how the infection will spread and how to limit the outbreak. We have developed a modified SEIR compartmental model with nine compartments (CoVCom9) to describe the dynamics of SARS-CoV-2 transmission in Ghana. We have carried out a detailed mathematical analysis of the CoVCom9, including the derivation of the basic reproduction number, R 0 . In particular, we have shown that the disease-free equilibrium is globally asymptotically stable when R 0 < 1 via a candidate Lyapunov function. Using the SARS-CoV-2 reported data for confirmed-positive cases and deaths from March 13 to August 10, 2020, we have parametrised the CoVCom9 model. The results of this fit show good agreement with data. We used Latin hypercube sampling-rank correlation coefficient (LHS-PRCC) to investigate the uncertainty and sensitivity of R 0 since the results derived are significant in controlling the spread of SARS-CoV-2. We estimate that over this five month period, the basic reproduction number is given by R 0 = 3 . 110 , with the 95% confidence interval being 2 . 042 ≤ R 0 ≤ 3 . 240 , and the mean value being R 0 = 2 . 623 . Of the 32 parameters in the model, we find that just six have a significant influence on R 0 , these include the rate of testing, where an increasing testing rate contributes to the reduction of R 0 .


The human placental methylome.
This review provides an overview of the unique features of DNA methylation in the human placenta. We discuss the importance of understanding placental development, structure, and function in the interpretation of DNA methylation data. Examples are given of how DNA methylation is important in regulating placental-specific gene expression, including monoallelic expression and X-chromosome inactivation in the placenta. We also discuss studies of global DNA methylation changes in the context of placental pathology and environmental exposures.


Observations on the prenatal development of human lymphatic vessels with focus on basic structural elements of lymph flow.
The prenatal development of human lymphatic systems has not attracted enough attention by lymphatic researchers in the past. Yet clearly these critical, early events determine the fate and function of the human lymphatic system. The main focus of these studies was to investigate the embryonic development of human lymphangions including lymphatic valves and muscle cells, to better understand the prenatal formation of basic structural elements of lymph flow. This review in most of its parts is a short summary of the findings. It provides important information necessary for understanding the development and functioning of the human lymphatic system. The structural basis of the active lymph transport system--the lymphatic muscle cells and lymphatic valves--which is absolutely necessary for all functions of lymphatic system, is already formed during the first half of the prenatal development in humans. During the second half of this development maturation of this system is already underway. The enlargement of lymphatic muscle cells together with increases in their quantity leads to formation of the multi-layered lymphatic vessel wall, able to develop contractions strong enough to propel lymph downstream of the lymphatic channels against gravity in bipedal humans. The development of the competent valves in lymphatic vessels occurs at the same time creating the ground for effective net, unidirectional lymph flow. The data summarized here represents some of the first systematic studies of the prenatal development of lymphatic muscle cells and valves in humans.


Defective hepatitis B virus DNA is not associated with disease status but is reduced by polymerase mutations associated with drug resistance.
Defective hepatitis B virus DNA (dDNA) is reverse-transcribed from spliced hepatitis B virus (HBV) pregenomic messenger RNA (pgRNA) and has been identified in patients with chronic HBV (CH-B). The major 2.2-kb spliced pgRNA encodes a novel HBV gene product, the hepatitis B splice protein (HBSP) via a deletion and frame shift within the polymerase. Although spliced RNA and HBSP expression have been associated with increased HBV DNA levels and liver fibrosis, the role of dDNA in HBV-associated disease is largely undefined. Our aims were to (1) compare the relative proportions of dDNA (% dDNA) in a range of HBV-infected serum samples, including patients with human immunodeficiency virus (HIV)/HBV coinfection and HBV-monoinfected persons with differing severities of liver disease, and (2) determine the effect of mutations associated with drug resistance on defective DNA production. Defective DNA was detected in 90% of persons with CH-B. There was no significant difference in the relative abundance of dDNA between the monoinfected and HIV/HBV-coinfected groups. We also found no association between the % dDNA and alanine aminotransferase, hepatitis B e antigen status, HBV DNA levels, fibrosis levels, compensated or decompensated liver cirrhosis, genotype, or drug treatment. However, the % dDNA was significantly lower in individuals infected with lamivudine-resistant (LMV-R) HBV compared with wild-type HBV (P < 0.0001), indicating that antiviral drug resistance alters the balance between defective and genomic length DNA in circulation. Experiments in vitro using HBV encoding LMV-R mutations confirmed these results. Our results identified no association between dDNA and parameters associated with disease status and suggested that the relative abundance of dDNA is largely dependent on the integrity of the HBV polymerase and is unrelated to the severity of liver disease.


Ewing Sarcoma, an enigmatic malignancy of likely progenitor cell origin, driven by transcription factor oncogenic fusions.
Since its first description by James Ewing in 1921, Ewing Sarcoma has been a cryptic malignancy. A poorly differentiated tumor of uncertain histogenesis and aggressive biologic behavior, it is the second most common malignancy of bone and soft tissue affecting adolescents and young adults. Some two decades ago, the understanding of Ewing Sarcoma biology took a leap forward with the identification of recurrent EWS/Ets fusions, which drive onco-genesis in this disease. A further leap forward occurred over the last half decade with the application of gene silencing, global expression profiling and primary cell culture technologies to the study of this disease. Resulting work has revealed EWS/Ets fusions to be surprisingly versatile regulators of gene expression, and has narrowed the search for the elusive cell of origin. Improved understanding of EWS/Ets biology and relevant oncogenic pathways has in turn led to the development of targeted therapies, including, recently, small molecules targeting key complexes involving the oncogenic fusion itself. In many respects still remaining an enigma, Ewing Sarcoma is an important model for cancers originating in progenitor-type cells or manifesting progenitor-type cell features, and cancers containing recurrent oncogenic fusions, the latter a surprisingly expanding number.


Epidemiology of non-steroidal anti-inflammatory drugs consumption in Spain. The MCC-Spain study.
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used despite their risk of gastrointestinal bleeding or cardiovascular events. We report the profile of people taking NSAIDs in Spain, and we include demographic factors, health-related behaviours and cardiovascular disease history. Four thousand sixtyparticipants were selected using a pseudorandom number list from Family Practice lists in 12 Spanish provinces. They completed a face-to-face computerized interview on their NSAID consumption, demographic characteristics, body mass index, alcohol and tobacco consumption and medical history. In addition, participants completed a self-administered food-frequency and alcohol consumption questionnaire. Factors associated with ever and current NSAID consumption were identified by logistic regression. Women consumed more non-aspirin NSAIDs (38.8% [36.7-41.0]) than men (22.3 [20.5-24.2]), but men consumed more aspirin (11.7% [10.3-13.2]) than women (5.2% [4.3-6.3]). Consumption of non-aspirin NSAIDs decrease with age from 44.2% (39.4-49.1) in younger than 45 to 21.1% (18.3-24.2) in older than 75, but the age-pattern for aspirin usage was the opposite. Aspirin was reported by about 11% patients, as being twice as used in men (11.7%) than in women (5.2%); its consumption increased with age from 1.7% (< 45 years old) to 12.4% (≥75 years old). Aspirin was strongly associated with the presence of cardiovascular risk factors or established cardiovascular disease, reaching odds ratios of 15.2 (7.4-31.2) in women with acute coronary syndrome, 13.3 (6.2-28.3) in women with strokes and 11.1 (7.8-15.9) in men with acute coronary syndrome. Participants with cardiovascular risk factors or diseases consumed as much non-aspirin NSAID as participants without such conditions. Non-aspirin NSAIDs were more consumed by women and aspirin by men. The age patterns of aspirin and non-aspirin NSAIDs were opposite: the higher the age, the lower the non-aspirin NSAIDs usage and the higher the aspirin consumption. People with cardiovascular risk factors or diseases consumed more aspirin, but they did not decrease their non-aspirin NSAIDs usage.


Hsmar1 transposition is sensitive to the topology of the transposon donor and the target.
Hsmar1 is a member of the Tc1-mariner superfamily of DNA transposons. These elements mobilize within the genome of their host by a cut-and-paste mechanism. We have exploited the in vitro reaction provided by Hsmar1 to investigate the effect of DNA supercoiling on transposon integration. We found that the topology of both the transposon and the target affect integration. Relaxed transposons have an integration defect that can be partially restored in the presence of elevated levels of negatively supercoiled target DNA. Negatively supercoiled DNA is a better target than nicked or positively supercoiled DNA, suggesting that underwinding of the DNA helix promotes target interactions. Like other Tc1-mariner elements, Hsmar1 integrates into 5'-TA dinucleotides. The direct vicinity of the target TA provides little sequence specificity for target interactions. However, transposition within a plasmid substrate was not random and some TA dinucleotides were targeted preferentially. The distribution of intramolecular target sites was not affected by DNA topology.


Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation: a randomized multicenter study.
This trial evaluated the efficacy and safety of the combination of antiplatelet and moderate-intensity anticoagulation therapy in patients with atrial fibrillation associated with recognized risk factors or mitral stenosis. Warfarin was more effective than aspirin in preventing stroke in these patients; combined therapy with low anticoagulant intensity was ineffective. Mitral stenosis patients were not investigated. We performed a multicenter randomized trial in 1,209 patients at risk. The intermediate-risk group included patients with risk factors or age >60 years: 242 received the cyclooxygenase inhibitor triflusal, 237 received acenocumarol, and 235 received a combination of both. The high-risk group included patients with prior embolism or mitral stenosis: 259 received anticoagulants and 236 received the combined therapy. Median follow-up was 2.76 years. Primary outcome was a composite of vascular death and nonfatal stroke or systemic embolism. Primary outcome was lower in the combined therapy than in the anticoagulant arm in both the intermediate- (hazard ratio [HR] 0.33 [95% confidence interval (CI)0.12 to 0.91]; p = 0.02) and the high-risk group (HR 0.51 [95% CI 0.27 to 0.96]; p = 0.03). Primary outcome plus severe bleeding was lower with combined therapy in the intermediate-risk group. Nonvalvular and mitral stenosis patients had similar embolic event rates during anticoagulant therapy. The combined antiplatelet plus moderate-intensity anticoagulation therapy significantly decreased the vascular events compared with anticoagulation alone and proved to be safe in atrial fibrillation patients.


Salutogenic effects of the environment: review of health protective effects of nature and daylight.
Both nature and daylight have been found to positively influence health. These findings were, however, found in two separate research domains. This paper presents an overview of effects found for daylight and nature on health and the health-related concepts stress, mood, and executive functioning and self-regulation. Because of the overlap in effects found and the co-occurrence of both phenomena, the paper points to the need to consider daylight factors when investigating effects of nature and vice versa. Furthermore, the existence of possibly shared underlying mechanisms is discussed and the need to unify the research paradigms and dependent variables used between the two research fields. Last, in view of the beneficial effects of both phenomena on health, our objective is to raise awareness amongst the general public, designers, and health practitioners to use these naturally available phenomena to their full potential.


Program integrity as a moderator of prevention program effectiveness: results for fifth-grade students in the adolescent alcohol prevention trial.
This study reports the results of a test of the quality of program delivery (program integrity) as a variable that may moderate the effectiveness of alcohol prevention programs. Two theory-based programs, Resistance Training and Normative Education, were delivered to fifth-grade students who were then tested on program relevant mediating variables. Resistance Training was found to improve students' knowledge of peer pressure resistance strategies, their performance on a behavioral assessment of peer pressure resistance skills and the manifestation of their future intentions to drink alcohol. Normative Education was found to improve students' perceptions of a conservative norm regarding alcohol use, facilitated their belief that refusing unwanted offers to drink alcohol could be easily accomplished and reduced their perceptions of the prevalence of alcohol use. Program integrity was measured by program specialists who taught the programs to students and by trained observers. Ratings of program integrity were found to significantly moderate outcomes for three of seven mediating variables. Affected were knowledge of peer pressure resistance strategies, behavioral pressure resistance skills and perceived self-efficacy. These results suggest that the quality of program delivery and reception may play an important moderating function on prevention program effectiveness.


Prevalence of enteric zoonotic agents in cats less than 1 year old in central New York State.
A prevalence study of several enteric zoonotic bacterial and parasitic infections was conducted in 263 fecal samples from cats that were between 1 and 12 months old, and that were in humane shelters (n = 149) or were presented to primary-care veterinarians (n = 114). Of these samples, 2 (0.8%) were positive for Campylobacter, 2 (0.8%) were positive for Salmonella, and 10 (3.8%) were positive for Cryptosporidium, confirming that these zoonotic agents are relatively rare in cats. Toxocara cati (33.0%) and Giardia (7.3%) were found more commonly. At least 1 zoonotic agent was detected in 105 samples (40.7%). Our results suggest that clinical signs such as diarrhea are not reliable predictors of whether a cat is actively shedding enteric organisms. Therefore, the decision to test a newly adopted cat should be based on the potential risks to the client rather than on the cat's clinical presentation. The high prevalence of T. cati confirms that comprehensive testing or treatment for ascarids is warranted in newly adopted kittens.


Role of topical magnesium in post-operative sore throat: A systematic review and meta-analysis of randomised controlled trials.
Post-operative sore throat (POST) is a common undesirable consequence of tracheal intubation. Magnesium, an N-methyl-D-aspartate receptor antagonist, has anti-nociceptive and anti-inflammatory properties, and has been found to be useful in POST prevention in various trials. We conducted this systematic review and meta-analysis to study the efficacy of topical magnesium in preventing POST in adult patients undergoing surgery under general anaesthesia with single lumen tracheal tube. Comprehensive literature search was performed in PubMed, Google Scholar, EMBASE, Scopus and the Cochrane central registers of controlled trial databases through July, 2018 and data were pooled using fixed effect modelling followed by random-effect methods (after assessing heterogeneity with fixed modelling). The primary outcome was the incidence of POST at 24 h after surgery/extubation. Comparative results were deliberated as pooled mean difference for continuous variables and Mantel-Haenszel (MH) odds ratio for dichotomous variables. Statistical analysis was done using Comprehensive Meta-Analysis-Version 3 (Biostat Inc., USA). Seven trials involving 726 study participants were included in the final analysis. Incidence of POST at 24 hours was significantly lower in magnesium group (26/363) in comparison to active and non-active control group (89/363); P = 0.00- RR 0.22 (95%CI = 0.12-0.39, I2 = 0%). No significant adverse events were reported with the use of topical magnesium. Prophylactic use of topical magnesium before the induction of general anaesthesia seems to be an effective measure to decrease the incidence of POST.


Protective effect of rutin on the antioxidant genes expression in hypercholestrolemic male Westar rat.
High-cholesterol diet (HCD) increases the oxidative stress in different tissues leading to many diseases. Rutin (RT) is a natural flavonoid (vitamin p), which possesses an antioxidant activity with protective potential. The present study aimed to examine the potential effects of rutin on hypercholesterolemia-induced hepatotoxicity in rat. Male Wistar rats were divided into four groups: GI) control (Rat chow), GII) Rutin (0.2% in rat chow), GIII) HCD (1% cholesterol and 0.5% cholic acid in rat chow) and GIV) rutin (0.2%) + HCD. Rutin in combination with HCD induced a significant protective effect against the hepatotoxicity by reducing the plasma level of alanine transaminase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL). The HCD (GII) showed a decrease in glutathione peroxidase (GPx), glutathione reductase (GR) and increase in glutathione S transferase α (GSTα), sulfiredoxin-1(Srx1), glutamate-cysteine ligase (GCL) and paraoxonase-1(PON-1) genes expression levels. Treatment with rutin reversed all the altered genes induced by HCD nearly to the control levels. The present study concluded that the HCD feedings altered the expression levels of some genes involved in the oxidative stress pathway resulting in DNA damage and hepatotoxicity. Rutin have a hepatoprotective effect through the mechanism of enhancing the antioxidant effect via amelioration of oxidative stress genes.


Myoferlin depletion elevates focal adhesion kinase and paxillin phosphorylation and enhances cell-matrix adhesion in breast cancer cells.
Breast cancer is the second leading cause of malignant death among women. A crucial feature of metastatic cancers is their propensity to lose adhesion to the underlying basement membrane as they transition to a motile phenotype and invade surrounding tissue. Attachment to the extracellular matrix is mediated by a complex of adhesion proteins, including integrins, signaling molecules, actin and actin-binding proteins, and scaffolding proteins. Focal adhesion kinase (FAK) is pivotal for the organization of focal contacts and maturation into focal adhesions, and disruption of this process is a hallmark of early cancer invasive potential. Our recent work has revealed that myoferlin (MYOF) mediates breast tumor cell motility and invasive phenotype. In this study we demonstrate that noninvasive breast cancer cell lines exhibit increased cell-substrate adhesion and that silencing of MYOF using RNAi in the highly invasive human breast cancer cell line MDA-MB-231 also enhances cell-substrate adhesion. In addition, we detected elevated tyrosine phosphorylation of FAK (FAK(Y397)) and paxillin (PAX(Y118)), markers of focal adhesion protein activation. Morphometric analysis of PAX expression revealed that RNAi-mediated depletion of MYOF resulted in larger, more elongated focal adhesions, in contrast to cells transduced with a control virus (MDA-231(LVC) cells), which exhibited smaller focal contacts. Finally, MYOF silencing in MDA-MB-231 cells exhibited a more elaborate ventral cytoskeletal structure near focal adhesions, typified by pronounced actin stress fibers. These data support the hypothesis that MYOF regulates cell adhesions and cell-substrate adhesion strength and may account for the high degree of motility in invasive breast cancer cells.


A freshwater radiation of diplonemids.
Diplonemids are considered marine protists and have been reported among the most abundant and diverse eukaryotes in the world oceans. Recently we detected the presence of freshwater diplonemids in Japanese deep freshwater lakes. However, their distribution and abundances in freshwater ecosystems remain unknown. We assessed abundance and diversity of diplonemids from several geographically distant deep freshwater lakes of the world by amplicon-sequencing, shotgun metagenomics and catalysed reporter deposition-fluorescent in situ hybridization (CARD-FISH). We found diplonemids in all the studied lakes, albeit with low abundances and diversity. We assembled long 18S rRNA sequences from freshwater diplonemids and showed that they form a new lineage distinct from the diverse marine clades. Freshwater diplonemids are a sister-group to a marine clade, which are mainly isolates from coastal and bay areas, suggesting a recent habitat transition from marine to freshwater habitats. Images of CARD-FISH targeted freshwater diplonemids suggest they feed on bacteria. Our analyses of 18S rRNA sequences retrieved from single-cell genomes of marine diplonemids show they encode multiple rRNA copies that may be very divergent from each other, suggesting that marine diplonemid abundance and diversity both have been overestimated. These results have wider implications on assessing eukaryotic abundances in natural habitats by using amplicon-sequencing alone.


Needle-Free Jet Injector-Assisted Triamcinolone Treatment of Keloids and Hypertrophic Scars is Effective and Well Tolerated in Children.
Keloids and hypertrophic scars can cause severe pain, pruritus, and psychological distress. Conventional intralesional corticosteroid treatment with needle injections remains challenging, especially in children with needle phobia. We aimed to evaluate the effectiveness, tolerability, and patient satisfaction of intralesional treatment with triamcinolone acetonide using a needle-free electronic pneumatic jet injector in children with keloids and hypertrophic scars. A retrospective study was performed in children with keloids and hypertrophic scars who received intralesional triamcinolone acetonide treatments using an electronic pneumatic jet injector. Effectiveness was evaluated using the Patient and Observer Scar Assessment Scale and Global Aesthetic Improvement Score at follow-up versus baseline. Tolerability was assessed with reported adverse effects and injection-related pain using a visual analog scale. Satisfaction questionnaires were used to evaluate treatment-related patient satisfaction. Six female patients and five male patients aged 5-17 years, with a total of >118 keloids or hypertrophic scars were included. Electronic pneumatic jet injector treatment led to a significant reduction in the total Patient and Observer Scar Assessment Scale observer and patient scores compared with baseline, with a median reduction of 28.9% and 23.8%, respectively (p = 0.005; p = 0.009). Median visual analog scale pain scores for electronic pneumatic jet injector treatment were significantly lower compared with needle injections, 3.0 versus 7.0, respectively (p = 0.027). No severe adverse effects were reported. Overall, 6 patients were 'satisfied' and five patients were 'very satisfied' with the treatment. Electronic pneumatic jet injector-assisted intralesional triamcinolone acetonide is an effective and well-tolerated treatment for keloids and hypertrophic scars in children. It should be considered as an alternative non-traumatic delivery method, especially in children with needle phobia or severe pain during previous needle injections.


Effects of Toona sinensis Leaf Extract and Its Chemical Constituents on Xanthine Oxidase Activity and Serum Uric Acid Levels in Potassium Oxonate-Induced Hyperuricemic Rats.
Toona sinensis leaf is used as a seasonal vegetable in Korea. A 70% ethanol extract of these leaves exhibited potent xanthine oxidase (XO) inhibition, with a 50% inhibitory concentration (IC50) of 78.4 µM. To investigate the compounds responsible for this effect, bioassay-guided purification led to the isolation of five constituents, identified as quercetin-3-O-rutinoside, quercetin-3-O-β-d-glucopyranoside, 1,2,3,4,6-penta-O-galloyl-β-d-glucopyranose (compound 3), quercetin-3-O-α-l-rhamnopyranoside, and kaempferol-3-O-α-l-rhamnopyranoside. Compound 3 showed the most potent inhibition of XO, with an IC50 of 2.8 µM. This was similar to that of allopurinol (IC50 = 2.3 µM), which is used clinically to treat hyperuricemia. Kinetic analyses found that compound 3 was a reversible noncompetitive XO inhibitor. In vivo, the T. sinensis leaf extract (300 mg/kg), or compound 3 (40 mg/kg), significantly decreased serum uric acid levels in rats with potassium oxonate-induced hyperuricemia. Furthermore, ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry analysis identified a high level of compound 3 in the leaf extract. These findings suggest that T. sinensis leaves could be developed to produce nutraceutical preparations.


Factors influencing psychological distress during a disease epidemic: data from Australia's first outbreak of equine influenza.
In 2007 Australia experienced its first outbreak of highly infectious equine influenza. Government disease control measures were put in place to control, contain, and eradicate the disease; these measures included movement restrictions and quarantining of properties. This study was conducted to assess the psycho-social impacts of this disease, and this paper reports the prevalence of, and factors influencing, psychological distress during this outbreak. Data were collected using an online survey, with a link directed to the affected population via a number of industry groups. Psychological distress, as determined by the Kessler 10 Psychological Distress Scale, was the main outcome measure. In total, 2760 people participated in this study. Extremely high levels of non-specific psychological distress were reported by respondents in this study, with 34% reporting high psychological distress (K10 > 22), compared to levels of around 12% in the Australian general population. Analysis, using backward stepwise binary logistic regression analysis, revealed that those living in high risk infection (red) zones (OR = 2.00; 95% CI: 1.57-2.55; p < 0.001) and disease buffer (amber) zones (OR = 1.83; 95% CI: 1.36-2.46; p < 0.001) were at much greater risk of high psychological distress than those living in uninfected (white zones). Although prevalence of high psychological distress was greater in infected EI zones and States, elevated levels of psychological distress were experienced in horse-owners nationally. Statistical analysis indicated that certain groups were more vulnerable to high psychological distress; specifically younger people, and those with lower levels of formal educational qualifications. Respondents whose principal source of income was from horse-related industry were more than twice as likely to have high psychological distress than those whose primary source of income was not linked to horse-related industry (OR = 2.23; 95% CI: 1.82-2.73; p < 0.001). Although, methodologically, this study had good internal validity, it has limited generalisability because it was not possible to identify, bound, or sample the target population accurately. However, this study is the first to collect psychological distress data from an affected population during such a disease outbreak and has potential to inform those involved in assessing the potential psychological impacts of human infectious diseases, such as pandemic influenza.


The effect of video-based fistula care education on hemodialysis patients' self-care behaviors: A randomized controlled study.
This study aimed to determine the effect of face-to-face and video-based education for fistula care on hemodialysis patients' self-care behaviors. The study was conducted as a randomized controlled experimental study. Accordingly, 60 patients were included in the study for 95% strength. Fistula care training was given to the patients in the control group using face-to-face education technique. Fistula care training was given to the patients in the experimental group using a video-based technique. The analysis showed that the post-test second week (p = 0.044) and fourth week (p = 0.00) mean scores of the experimental group were higher compared to those of the control group. These results showed that the video-based education given to hemodialysis patients was more memorable and instructive than the verbal education, and it was observed that the video-based education showed a higher level of success in developing self-care skills.


Susceptibility of Chicken Embryos, Sheep, Cattle, Pigs, and Chickens to Zika Virus Infection.
The susceptibility of sheep, cattle, pigs, chickens and chicken embryos to Zika virus infection was evaluated by experimental inoculation with Zika virus Thailand strain isolated from a Canadian traveler in 2013. The inoculated animals did not develop any clinical signs of disease nor evidence of Zika virus replication in peripheral blood, cerebrospinal fluid and tissues including brain and spinal cord assessed by real-time RT-PCR. Sera were also negative for Zika virus antibodies by Zika virus neutralization assays as well as Zika virus immunoperoxidase staining of Zika infected Vero cells. Chicken embryos were inoculated by different routes including yolk sac (4 day old embryos), chorioallantoic membrane (8 day old embryos), amniotic fluid (8 day old embryos) and intravenous routes (12 day old embryos). Virus replication in chicken embryos was observed in the brain and body tissues following intravenous (IV), yolk sac (YS), chorioallantoic membrane (CAM), and amniotic fluid (AF) inoculation routes. The highest mortality was observed in embryos inoculated via yolk sac. The dead embryos showed diffuse muscular hemorrhages. The yolk sac inoculated chicken embryos showed delayed hatching and displayed neurological signs immediately after hatching. These studies demonstrate that 8 week old sheep, 6 month old cattle, 4 week old pigs, and 4 week old chickens are not susceptible to Zika virus infection when inoculated experimentally and therefore unlikely to pose a risk as Zika virus reservoirs. However, chicken embryos are highly susceptible to Zika virus resulting in clinical disease of chicks after hatching. This study demonstrates that Zika virus has a tropism for embryonic tissue and that chicken embryos can be used as a model to study Zika virus replication and pathogenesis.


A community-based study of chronic fatigue syndrome.
Most previous estimates of the prevalence of chronic fatigue syndrome (CFS) have derived largely from treated populations, and have been biased by differential access to health care treatment linked with sex, ethnic identification, and socioeconomic status. To assess the point prevalence of CFS in an ethnically diverse random community sample. A sample of 28,673 adults in Chicago, Ill, was screened by telephone, and those with CFS-like symptoms were medically evaluated. MAIN OUTCOME MEASURES AND ANALYSES: Self-report questionnaires, psychiatric evaluations, and complete medical examinations with laboratory testing were used to diagnose patients with CFS. Univariate and multivariate statistical techniques were used to delineate the overall rate of CFS in this population, and its relative prevalence was subcategorized by sex, ethnic identification, age, and socioeconomic status. There was a 65.1% completion rate for the telephone interviews during the first phase of the study. Findings indicated that CFS occurs in about 0.42% (95% confidence interval, 0.29%-0.56%) of this random community-based sample. The highest levels of CFS were consistently found among women, minority groups, and persons with lower levels of education and occupational status. Chronic fatigue syndrome is a common chronic health condition, especially for women, occurring across ethnic groups. Earlier findings suggesting that CFS is a syndrome primarily affecting white, middle-class patients were not supported by our findings.


Influence of glucose infusions on luteinizing hormone secretion in the energy-restricted, primiparous, lactating sow.
The objective of this experiment was to evaluate the influence of glucose infusion during lactation on LH secretion in the energy-restricted sow. Ten primiparous Landrace x Yorkshire sows (152 kg postfarrowing) were fed a low-energy (6.5 Mcal of ME/d), high-lysine (45 g/d), corn-soybean meal diet throughout lactation. On d 18 of lactation, sows received a continuous infusion (1 L/12 h) of glucose (50% dextrose solution) or .9% saline from 1200 to 2400. Blood samples were drawn every 15 min for an 18-h period on d 18 to evaluate concentrations of plasma glucose, serum insulin, and serum LH before (600 to 1200) and during (1215 to 2400) the infusions. The glucose infusion immediately increased (P less than .001) plasma glucose and serum insulin relative to preinfusion levels. Glucose and insulin concentrations in sows receiving the glucose infusion were higher (P less than .001) throughout the infusion period relative to concentrations in sows receiving a saline infusion. Glucose infusions had no influence on LH pulsatility during the 12-h infusion period. In contrast to the response observed in the nutrient-restricted gilt, these results indicate that glucose infusions do not result in an immediate increase in pulsatile LH secretion in the energy-restricted, lactating sow.


Effects of KRN4884, a novel K+ channel opener, on ionic currents in rabbit femoral arterial myocytes.
Effects of KRN4884 (5-amino-N-[2-(2-chlorophenyl)ethyl]-N'-cyano-3-pyridinecarboxamidine), a novel K(+) channel opener, on ionic currents were examined in rabbit femoral arterial myocytes (RFAMs). Under whole-cell clamp conditions where cells were superfused with 5.9 mM K(+) bathing solution, KRN4884 elicited an outward current at -30 mV. KRN4884-induced current had a reversal potential of -78 mV and was abolished by application of glibenclamide (glib). KRN4884 was approximately 43 times more potent than levcromakalim in activating an ATP-sensitive K(+) current (I(K-ATP)). On the other hand, KRN4884 affected neither voltage-dependent Ca(2+) nor delayed rectifier K(+) channel currents. In the inside-out patch clamp configuration where cells were superfused with the symmetrical 140 mM K(+) solution, KRN4884 activated 47 pS K(+) channels in the presence of adenosine diphosphate. Similar 47 pS K(+) channels, which were reversibly inhibited by glib, were recorded under outside-out patch conditions. Using RT-PCR analysis, we found that inward rectifier K channel 6.1 (Kir6.1) and sulfonylurea 2B (SUR2B) transcripts were predominantly expressed in rabbit femoral artery. These results indicate that KRN4884 potently activates I(K-ATP) in RFAMs. The KRN4884-sensitive 47 pS K(+) channel activity underlying I(K-ATP) is a vascular type K(ATP) channel consisting of Kir6.1 and SUR2B and has similar characteristics to those of ATP-sensitive K(+) channels activated by K(+) channel openers in other types of smooth muscles.


[Acquired immune thrombocytopenia: An update on aspects of diagnosis and management relevant for intensive care medicine].
Acquired thrombocytopenias represent a group of bleeding diseases, which can be mediated by immune or non-immune factors. Acquired immune thrombocytopenia (AITP) leads to an accelerated decrease in platelet count by platelet reactive antibodies arising from several mechanisms. In AITP, autoantibodies, alloantibodies or drug-dependent antibodies are usually targeting platelet surface glycoproteins. The consequence of this is a significant decrease in the number of circulating platelets, leading to clinic pathological disorders including immune thrombocytopenia, heparin-induced thrombocytopenia or drug-induced thrombocytopenia, respectively. The aforementioned disorders are characterized by a severe reduction in platelet count (< 20 × 109/l), which is, with the exception of HIT, associated with high bleeding risk. In this review we provide current insight into recent achievements regarding diagnosis and management of AITP.


[Usefulness of CA 15-3 for ten years follow-up of a patient with invasive breast cancer].
This clinical report illustrates the usefulness of routine CA 15.3 assay during the follow-up of patients treated for invasive breast cancer. This patient presented an isolated elevation of CA 15.3 eighteen months after initial treatment of inflammatory breast cancer. The scientific committee for breast cancer decided to modify the hormonotherapy, even without clinical or radiological event (tomodensitometry, echography, scintigraphy). The prompt CA 15.3 normalization persisted for more than seven years. When CA 15.3 levels increased again, a positron emission tomodensitometry was performed and revealed pulmonary nodes. The sole modification of hormone treatment, based upon isolated increase of CA 15.3, led to seven years of clinical and biological stability for our patient with probable pulmonary metastases.


A "clean cigarette" for a clean nation: a case study of Salem Pianissimo in Japan.
To illustrate, through internal industry documents, how RJ Reynolds exploited the concerns of the Japanese society about cleanliness to market the concept of cleaner, implicitly healthier cigarettes in Japan. Systematic keyword and opportunistic website searches of formerly private internal industry documents. Industry documents show that RJ Reynolds developed marketing plans based upon their cultural assumptions of Japanese people as fastidious about hygiene and manners, and with relatively high penchants to try new products. RJ Reynolds found there was also a growing concern for health, the environment, and smokers were conscious about annoying others. Deodorised consumer products were one of Japan's biggest trends. These characteristics presented RJ Reynolds with a profitable formula for marketing Salem Pianissimo, a clean cigarette with less smell and smoke. Salem Pianissimo, a 100 mm cigarette claiming to contain 1 mg tar and 0.1 mg nicotine, targeted women since menthol cigarettes were popular among 18-24 year old female smokers, although Japan's law prohibited those below 20 years to smoke and the tobacco industry had a voluntary code disallowing advertising to women and youth. RJ Reynolds successfully launched its clean cigarette, Salem Pianissimo, in Japan aiming to exploit perceived cultural characteristics such as a penchant for cleanliness, an eagerness to try new products, and social harmony.


Clinics in diagnostic imaging. 158. Duodenal ectopic pancreas.
A 46-year-old man presented with right loin tenderness following a road traffic accident. Computed tomography and magnetic resonance imaging showed a well-defined, smooth, enhancing oval lesion in the wall of the first part of the duodenum. The lesion was seen separately from the normal pancreas. It showed attenuation, intensity and enhancement similar to that of normal pancreas. Based on the imaging appearance, a diagnosis of ectopic pancreas was made. The patient underwent oesophagogastroduodenoscopy, endoscopic ultrasonography and fine-needle aspiration cytology of the lesion, which confirmed ectopic pancreatic tissue. Since the patient was asymptomatic, surgical resection was deferred. The embryologic origin, various locations, imaging appearance and clinical significance of ectopic pancreas are discussed.


The genetics of highly pathogenic avian influenza viruses of subtype H5 in Germany, 2006-2020.
The H5 A/Goose/Guangdong/1/1996 (gs/GD) lineage emerged in China in 1996. Rooted in the respective gs/GD lineage, the hemagglutinin (HA) gene of highly pathogenic avian influenza viruses (HPAIV) has genetically diversified into a plethora of clades and subclades and evolved into an assortment of sub- and genotypes. Some caused substantial losses in the poultry industry and had a major impact on wild bird populations alongside public health implications due to a zoonotic potential of certain clades. After the primary introduction of the HPAI H5N1 gs/GD lineage into Europe in autumn 2005 and winter 2005/2006, Germany has seen recurring incursions of four varying H5Nx subtypes (H5N1, H5N8, H5N5, H5N6) carrying multiple distinct reassortants, all descendants of the gs/GD virus. The first HPAIV H5 epidemic in Germany during 2006/2007 was caused by a clade 2.2 subtype H5N1 virus. Phylogenetic analysis confirmed three distinct clusters belonging to clades 2.2.1, 2.2.2 and 2.2, concurring with geographic and temporal structures. From 2014 onwards, HPAIV clade 184.108.40.206 has dominated the epidemiological situation in Germany. The initial clade 22.214.171.124a HPAIV H5N8, reaching Germany in November 2014, caused a limited epidemic affecting five poultry holdings, one zoo in Northern Germany and few wild birds. After November 2016, HPAIV of clade 22.214.171.124b have dominated the situation to date. The most extensive HPAIV H5 epidemic on record reached Germany in winter 2016/2017, encompassing multiple incursion events with two subtypes (H5N8, H5N5) and entailing five reassortants. A novel H5N6 clade 126.96.36.199b strain affected Germany from December 2017 onwards, instigating low-level infection in smallholdings and wild birds. Recently, in spring 2020, a novel incursion of a genetically distinct HPAI clade 18.104.22.168b H5N8 virus caused another epidemic in Europe, which affected a small number of poultry holdings, one zoo and two wild birds throughout Germany.


Emergence of cationic polyamine dendrimersomes: design, stimuli sensitivity and potential biomedical applications.
For decades, self-assembled lipid vesicles have been widely used in clinics as nanoscale delivery systems for various biomedical applications, including treatment of various diseases. Due to their core-shell architecture and versatile nature, they have been successfully used as carriers for the delivery of a wide range of therapeutic cargos, including drugs and nucleic acids, in cancer treatment. Recently, surface-modified polyamine dendrimer-based vesicles, or dendrimersomes, have emerged as promising alternatives to lipid vesicles for various biomedical applications, due to their ease of synthesis, non-immunogenicity, stability in circulation and lower size polydispersity. This mini-review provides an overview of the recent advances resulting from the use of biomimetic hydrophobically-modified polyamine-based dendrimersomes towards biomedical applications, focusing mainly on the two most widely used polyamine dendrimers, namely polyamidoamine (PAMAM) and poly(propylene imine) (PPI) dendrimers.


"In vitro" azathioprine-induced changes in peripheral T cell apoptosis and IFN-γ production associate with drug response in patients with Crohn's Disease.
The use of the highly effective thiopurines as early therapeutic option in Crohn's Disease (CD) may be discouraged by the long time interval required to obtain clinical efficacy as also by their potential side effects. The development of non-invasive markers of responsiveness to thiopurines represents a major attempt in the clinical management of CD patients. Azathioprine is able to induce apoptosis of T cells. We studied the effect of thiopurines on "in vitro" T cell apoptosis, IFN-γ and IL-10 production in a group of CD patients with known response to a previous treatment with AZA. Heparinized blood samples were drawn from 25 CD patients showing or not a previous responsiveness to a conventional azathioprine treatment (n=17 and n=8, respectively). CD4+ T cells were stimulated "in vitro" with aCD3/28 mAbs in the presence or absence of azathioprine, 6-mercaptopurine or 6-thioguanine. Apoptosis was assessed using Annexin V staining, and IFN-γ and IL-10 production in cell culture supernatants was evaluated by ELISA. Apoptosis stimulation index (% of apoptotic cells in the presence of thiopurine/% of apoptotic cells in the absence of thiopurine) and IFN-γ stimulation index (IFN-γ production in the presence of thiopurine/IFN-γ production in the absence of thiopurine) were, respectively, significantly lower and higher in non-responder when compared to responder patients. No variation was observed in IL-10 production. Evaluation of apoptosis and IFN-γ stimulation index of peripheral CD4+ T cell may be useful for a proper selection of CD patients candidate to thiopurine treatment.


The epidemiology of herpes zoster and potential cost-effectiveness of vaccination in England and Wales.
The epidemiology of herpes zoster and post-herpetic neuralgia (PHN) was quantified from a variety of data sources and the potential cost-effectiveness of vaccination assessed. The annual incidence and severity of zoster increases sharply with age, as measured by physician consultation and hospitalisation rates, average length of stay, average proportion of cases developing PHN and the age-specific case-fatality ratio. Combining these data with information on health related quality of life results in an estimated loss of 20000 quality adjusted life years (QALYs) annually in England and Wales from herpes zoster (17400 due to PHN). The current cost of treating herpes zoster associated disease is estimated to be 47.6m pounds annually. Since both the health and economic burden are high, vaccination of the elderly is expected to be cost-effective under most scenarios, the attractiveness of immunisation increasing with age due to the increased burden of disease in the very elderly.


Protein kinase A inhibition facilitates the antitumor activity of xanthohumol, a valosin-containing protein inhibitor.
Xanthohumol (XN), a simple prenylated chalcone, can be isolated from hops and has the potential to be a cancer chemopreventive agent against several human tumor cell lines. We previously identified valosin-containing protein (VCP) as a target of XN; VCP can also play crucial roles in cancer progression and prognosis. Therefore, we investigated the molecular mechanisms governing the contribution of VCP to the antitumor activity of XN. Several human tumor cell lines were treated with XN to investigate which human tumor cell lines are sensitive to XN. Several cell lines exhibited high sensitivity to XN both in vitro and in vivo. shRNA screening and bioinformatics analysis identified that the inhibition of the adenylate cyclase (AC) pathway synergistically facilitated apoptosis induced by VCP inhibition. These results suggest that there is crosstalk between the AC pathway and VCP function, and targeting both VCP and the AC pathway is a potential chemotherapeutic strategy for a subset of tumor cells.


Personal Agency and Community Resilience: Narratives of Women Navigating Health Care With Chronic Lyme Disease.
Chronic Lyme disease can manifest as a debilitating illness with symptoms that change over time. With its varied presentation, timeline variation, diagnostic difficulty, and lack of definitive treatment, clinical recognition of chronic Lyme disease remains controversial. At the same time, patients face challenges in finding a provider who is supportive and knowledgeable about diagnosing and treating Lyme. We examined the ways the medical system may have affected the lived experiences of chronic Lyme patients. In this article, we communicate the personal, health care, and community illness experiences of 14 women navigating the medical system with chronic Lyme disease through a qualitative community-based participatory research study using interviews and narrative reflection in a rural community setting. The women were interviewed by a researcher living with chronic Lyme disease and the transcripts were analyzed for themes. All participants described navigating multiple allopathic and nonallopathic care modalities to find satisfactory care. They struggled with physical and emotional burdens of chronic, nonlinear illness, as well as disbelief and discrimination by medical providers. Their lives followed patterns of illness and wellness, trust and mistrust of medical treatment, and community connection and disengagement. They learned to become their own advocates to seek affirmative care. They are aware of the controversial nature of their illness, and many have channeled their frustrations into caring for one another through their Lyme community. Women living with controversial diagnoses like chronic Lyme disease experience increased challenges navigating the medical system to find satisfactory care and thus create communities with each other for mutual aid and support. In understanding these challenges, the medical community can improve care for people living with contested chronic illnesses.


Heat stress but not inbreeding affects offensive sperm competitiveness in Callosobruchus maculatus.
Environmental and genetic stress have well-known detrimental effects on ejaculate quality, but their concomitant effect on male fitness remains poorly understood. We used competitive fertilization assays to expose the effects of stress on offensive sperm competitive ability in the beetle Callosobruchus maculatus, a species where ejaculates make up more than 5% of male body mass. To examine the effects of environmental and genetic stress, males derived from outcrosses or sib matings were heat shocked at 50°C for 50 min during the pupal stage, while their siblings were maintained at a standard rearing temperature of 28°C. Heat-shocked males achieved only half the offensive paternity success of their siblings. While this population exhibited inbreeding depression in body size, sperm competitiveness was unaffected by inbreeding, nor did the effect of heat shock stress on sperm competitiveness depend on inbreeding status. In contrast, pupal emergence success was increased by 34% among heat-stressed individuals, regardless of their inbreeding status. Heat-shocked males' ejaculate size was 19% reduced, but they exhibited 25% increased mating duration in single mating trials. Our results highlight both the importance of stress in postcopulatory sexual selection, and the variability among stressors in affecting male fitness.


AMPA receptor antagonists for the treatment of stroke.
Signal transduction via ionotropic glutamate receptors is found in many life forms, from protozoa to mammals. Glutamate is the main excitatory neurotransmitter in the mammalian CNS, were fast postsynaptic depolarisation is induced by the activation of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors. In addition to their important physiological role, excessive AMPA receptor stimulation is also a hallmark of excitotoxicity-related diseases, like ischaemic stroke. Conversely, AMPA receptor inhibitors were proposed to be useful neuroprotective drugs. First generation AMPA receptor blockers were competitive antagonists, like NBQX, which showed robust neuroprotection in a variety of disease-related animal models. Its clinical use, however, was restricted by the very low solubility, inducing kidney precipitaton in vivo. Second generation competitive antagonists are available, which do not possess this property. None of those, however, up to now is in clinical use. Competitive AMPA receptor antagonists are not the first choice for neuroprotective drugs, since due to receptor kinetics they preferently suppress the physiological relevant component of the postsynaptic glutamate response. Non-competitive blockers, like 2,3-benzodiazepines or the novel neuroprotectant BIIR 561 should be suited better for the treatment of stroke. The latter compound is also described as blocker of voltage-gated sodium channels. Targetting more than one mechanism in the excitotoxicity cascade might be a fruitful approach for the development of neuroprotective drugs.


Management of occupational exposures to hepatitis C virus: current practice and controversies.
Unlike hepatitis B virus and human immunodeficiency virus, there currently are no immunization or chemoprophylactic interventions available to prevent infection after an occupational exposure to hepatitis C virus (HCV). A "Reality Check" session was held at the 4th Decennial International Conference on Nosocomial and Healthcare-Associated Infections to gather information on current practices related to management of occupational exposures to HCV, generate discussion on controversial issues, and identify areas for future research. Infection control professionals in attendance were knowledgeable in most issues addressed regarding the management of occupational exposures to HCV. Areas of controversy included the use of antiviral therapy early in the course of HCV infection and the appropriate administrative management of an HCV-infected healthcare worker.


Conformational sampling of peptides in the presence of protein crowders from AA/CG-multiscale simulations.
Macromolecular crowding is recognized as an important factor influencing folding and conformational dynamics of proteins and nucleic acids. Previous views of crowding have focused on the mostly entropic volume exclusion effect of crowding, but recent studies are indicating the importance of enthalpic effects, in particular, changes in electrostatic interactions due to crowding. Here, temperature replica exchange molecular dynamics simulations of trp-cage and melittin in the presence of explicit protein crowders are presented to further examine the effect of protein crowders on peptide dynamics. The simulations involve a three-component multiscale modeling scheme where the peptides are represented at an atomistic level, the crowder proteins at a coarse-grained level, and the surrounding aqueous solvent as implicit solvent. This scheme optimally balances a physically realistic description for the peptide with computational efficiency. The multiscale simulations were compared with simulations of the same peptides in different dielectric environments with dielectric constants ranging from 5 to 80. It is found that the sampling in the presence of the crowders resembles sampling with reduced dielectric constants between 10 and 40. Furthermore, diverse conformational ensembles are generated in the presence of crowders including partially unfolded states for trp-cage. These findings emphasize the importance of enthalpic interactions over volume exclusion effects in describing the effects of cellular crowding.


GH treatment induces sustained catch-up growth in children with intrauterine growth retardation: 7-year results.
The anthropometric response to 7 years of GH treatment was assessed in 11 short children with Russell-Silver syndrome (RSS) and in 5 with non-dysmorphic intrauterine growth retardation (NRSS). GH treatment induced a significant increase (p < 0.0001) in the mean height standard deviation score (SDS) and at the 7-year follow-up a height appropriate for the natural history of final stature in NRSS/RSS was already attained. An appreciable growth rate was still present with final height being attained only in 2 girls. There was no significant change in height SDS for bone age. Multiple regression analysis showed only chronological age at the onset of GH treatment was a predictor of gain in height SDS during GH therapy. These findings suggest that early GH treatment improves long-term growth in children with NRSS/RSS. Moreover, final height attainment is required for a definitive assessment of the beneficial effect on adult stature. Bone age assessment is not a reliable parameter to predict final height outcome in these children.


Laser-induced breakdown spectroscopy (LIBS) of heavy metal ions at the sub-parts per million level in water.
We report a simple sub parts per million (sub-ppm) detection method for heavy metals in water by laser-induced breakdown spectroscopy (LIBS). Filter papers were used as the substrates for both transforming aqueous solutions to solid samples and for pre-concentrating dissolved heavy metal ions. The amount of sample uptake was 1.2 g by soaking a filter paper. This provides limit-of-detection (LOD) values of 2.7 and 0.36 ppm for Pb and Cr, respectively. The LODs could be improved remarkably by pre-concentrating the heavy metal ions. When a 40 g sample solution was evaporated on a filter paper, the LODs of 75 and 18 parts per billion (ppb) were obtained for Pb and Cr, respectively. Moreover, by either increasing the evaporated amount of sample solution or applying an argon gas flow, further improvement of the LODs was found to be very promising. The LIBS spectra of tap water were recorded using the pre-concentration method and are discussed in comparison with the results from inductively coupled plasma atomic emission spectroscopy (ICP-AES). We could observe strong emission lines of Ca, Mg, K, Cu, and Sr in the tap water, of which concentrations were determined to be 6.3, 1.3, 1.1, 0.64, and 0.046 ppm, respectively, by ICP-AES. Our method shows promise as a fast, reliable, water-quality monitoring tool for heavy-metal concentrations as well as for hardness.


Visuospatial attention lateralization in volleyball players and in rowers.
In the present study, differences in visuospatial attention lateralization were evaluated in athletes engaged in open-compared to closed-skill sports and sedentary nonathletes. 23 volleyball players (open skill; Italian national level and regional level), 10 rowers (closed skill, Italian national level), and 23 sedentary participants responded to a computerized line-length judgment task. Five lines, differing in the length of their right and left segments, were randomly presented; the respondent made a forced-choice decision about the respective length of the two segments. Volleyball players responded significantly faster; those at the higher competitive level were also more accurate, making a statistically significantly lower number of leftward errors as compared with rowers and controls. If such responses are due to training rather than self-selection of ability, then the results may suggest the possibility of changing the distribution of visuospatial attention by training in open-skill sports.


[The golden age of rheumatoid arthritis treatment].
Today, we enjoy the golden age of rheumatology. In the 1970s, the paradigm for treating rheumatoid arthritis consisted in a pyramid. In the decade of the 1980s, and shortly after began a revolution in the understanding and treatment of rheumatic diseases. Methotrexate and tumor necrosis factor-blockers came on the scene.


Frozen section diagnosis: an audit.
A consecutive series of 1000 operative frozen section diagnoses was reviewed. Correct diagnosis was made at the time in 96.5% of the cases. Clinically relevant errors were found in 1.3% of the cases and unimportant errors in 0.9%. Diagnosis was deferred, to await subsequent paraffin sections, in a further 1.3%. All the errors and provisional diagnoses in the deferred cases were conservative false negative results; no false positive diagnosis of malignancy was made. The cases of incorrect or deferred diagnosis were analysed to ascertain the origin of the difficulties, which comprised: technical imperfection (three cases); the focal nature of the lesion (14); and pathological misinterpretation (28). More than one of these factors played a part in eight cases. Further retrospective assessment indicated that the factors leading to error or deferred diagnosis were avoidable in 57% and potentially avoidable in 43% of cases. Misinterpretation was the single factor responsible for all avoidable misdiagnoses or deferred diagnosis. None the less, unavoidable factors led to erroneous or deferred diagnosis in about 2% of operative frozen section requests. Using present methods this seems to be the irreducible minimum of failures to make the correct diagnosis when frozen sections are assessed.


Lead Optimization Yields High Affinity Frizzled 7-Targeting Peptides That Modulate Clostridium difficile Toxin B Pathogenicity in Epithelial Cells.
Frizzled 7 (FZD7) receptors have been shown to play a central role in intestinal stem cell regeneration and, more recently, in Clostridium difficile pathogenesis. Yet, targeting FZD7 receptors with small ligands has not been explored as an approach to block C. difficile pathogenesis. Here, we report the discovery of high affinity peptides that selectively bind to FZD7 receptors. We describe an integrated approach for lead optimization, utilizing structure-based rational design and directed evolution, to enhance the peptide binding affinity while still maintaining FZD7 receptor selectivity. This work yielded new peptide leads with picomolar binding constants to FZD7 as measured by biophysical methods. The new peptides block the interaction between C. difficile toxin B (TcdB) and FZD receptors and perturb C. difficile pathogenesis in epithelial cells. As such, our findings provide a proof of concept that targeting FZD receptors could be a viable pharmacological approach to protect epithelial cells from TcdB pathogenicity.


Suspicious findings in antenatal care and their implications from the mothers' perspective: a prospective study in Germany.
Antenatal care services are well established in Germany, with at least 10 routine antenatal consultations per pregnancy. Although many individual antenatal screening procedures and tests have been assessed in clinical trials, little is known about the overall prevalence of suspicious findings in routine antenatal surveillance and about related effects on psychological maternal well-being. The objectives of this study were to evaluate the views of pregnant women on prevalence, type, and consequences of suspicious findings during antenatal care; to assess related worries and anxiety; and to compare the reports of risk factors by these women with the antenatal records. We enrolled 360 pregnant women participating in antenatal classes in the Rhein-Neckar area, Germany. They were followed up from the beginning of antenatal classes to the puerperium using self-administered structured questionnaires that covered previous antenatal consultations and related worries. The Spielberger State-Trait Anxiety Inventory was used to assess current and general levels of anxiety. Antenatal records were also analyzed. Postnatally, pregnancy outcomes were assessed by telephone interviews. Two-thirds (67.2%) of antenatal care attendees reported suspicious or abnormal findings, almost half of which (45.1%) resulted from routine ultrasound scans. More than half (53.2%) of those with suspicious findings reported that they were acutely worried. The suspected problem often did not materialize: 13 (81.3%) of 16 suspected malformations and 34 (81%) of 42 suspected growth-retarded babies were in the normal range. Many suspicious findings reported by mothers were not documented in the antenatal records. Contrary to their expectation of reassurance, most antenatal care attendees are warned about possible abnormalities, which often lead to further investigations and cause considerable worries. More research is needed to evaluate the long-term impact and consequences of suspicious or false screening results in routine antenatal care.


[The practice of breastfeeding counseling].
To provide health professionals with information on theory and practice of breastfeeding counseling. MEDLINE, Bireme library, Lilacs, relevant Internet websites, scientific journals, technical books, essays, theses, and national and international publications were selected, studied and used to provide information on the topic. The most important sources of data were: a publication by the World Health Organization (WHO - 1993) and the authors' experience and clinic practice in the assistance of mothers, children and families. A trained pediatrician plays a relevant role on increasing breastfeeding rates and its duration. To improve this performance, in 1993, WHO designed a 40-hour course using an important didactic strategy aimed at health professionals and mothers. The goal was to protect, promote and support maternal nursing. It is a professional way of dealing with the mother by listening and trying to understand her, offering her help on planning, taking decisions, and getting strength on how to deal with pressures, thus increasing her confidence and self-esteem. Scientific evidence proves the effectiveness of Breastfeeding Counseling. Moreover, health professional's knowledge and practice are very important to increase breastfeeding rates.


Common pathways of degenerative arthritis of the wrist.
Carpal arthrosis secondary to scapholunate advanced collapse is described in terms of pathomechanics, radiographic features, and treatment. In addition, a differential diagnosis of carpal arthrosis is presented. Emphasis is placed on the similarity of injury patterns observed in a variety of disease processes affecting the wrist.


Mother-to-fetus transmission of cytomegalovirus. A review.
Congenital human cytomegalovirus (CMV) infection is the leading infectious cause of mental retardation, sensorineural deafness and visual impairment. It is mainly related to a primary maternal infection. The placenta should be considered the most important site of both the protection of the fetus from CMV infection and the transmission of CMV from mother to fetus. The control of the passage of CMV across the placenta probably involves a cascade of regulatory events. Roles are played by factors relating to the host immune-selective pressures, such as local cytokines and maternal CMV-specific neutralizing antibodies. The presence of other pathogens at the maternal-fetal interface also influences the outcome of CMV infection. Further investigations are needed in which clinical CMV strains are applied in in vitro studies to unravel the molecular mechanism of the intrauterine transmission of CMV and to elucidate the complex regulation that leads to prevention of the in utero transmission of CMV in vivo.


A Physical Fatigue Evaluation Method for Automotive Manual Assembly: An Experiment of Cerebral Oxygenation with ARE Platform.
Due to the complexity of the automobile manufacturing process, some flexible and delicate assembly work relies on manual operations. However, high-frequency and high-load repetitive operations make assembly workers prone to physical fatigue. This study proposes a method for evaluating human physical fatigue for the manual assembly of automobiles with methods: NIOSH (National Institute for Occupational Safety and Health), OWAS (Ovako Working Posture Analysis System) and RULA (Rapid Upper Limb Assessment). The cerebral oxygenation signal is selected as an objective physiological index reflecting the human fatigue level to verify the proposed physical fatigue evaluation method. Taking auto seat assembly and automobile manual assembly as an example, 18 group experiments were carried out with the ARE platform (Augmented Reality-based Ergonomic Platform). Furthermore, predictions of metabolic energy expenditure were performed for experiments in Tecnomatix Jack. Finally, it is concluded that the proposed physical fatigue evaluation method can reflect the human physical fatigue level and is more accurate than the evaluation of metabolic energy consumption in Tecnomatix Jack because of the immersion that comes with the AR devices and the precision that comes with motion capture devices.


Rapid DNA Synthesis During Early Drosophila Embryogenesis Is Sensitive to Maternal Humpty Dumpty Protein Function.
Problems with DNA replication cause cancer and developmental malformations. It is not fully understood how DNA replication is coordinated with development and perturbed in disease. We had previously identified the Drosophila gene humpty dumpty (hd), and showed that null alleles cause incomplete DNA replication, tissue undergrowth, and lethality. Animals homozygous for the missense allele, hd272-9 , were viable, but adult females had impaired amplification of eggshell protein genes in the ovary, resulting in the maternal effects of thin eggshells and embryonic lethality. Here, we show that expression of an hd transgene in somatic cells of the ovary rescues amplification and eggshell synthesis but not embryo viability. The germline of these mothers remain mutant for the hd272-9 allele, resulting in reduced maternal Hd protein and embryonic arrest during mitosis of the first few S/M nuclear cleavage cycles with chromosome instability and chromosome bridges. Epistasis analysis of hd with the rereplication mutation plutonium indicates that the chromosome bridges of hd embryos are the result of a failed attempt to segregate incompletely replicated sister chromatids. This study reveals that maternally encoded Humpty dumpty protein is essential for DNA replication and genome integrity during the little-understood embryonic S/M cycles. Moreover, the two hd272-9 maternal-effect phenotypes suggest that ovarian gene amplification and embryonic cleavage are two time periods in development that are particularly sensitive to mild deficits in DNA replication function. This last observation has broader relevance for interpreting why mild mutations in the human ortholog of humpty dumpty and other DNA replication genes cause tissue-specific malformations of microcephalic dwarfisms.


Icariin attenuates the severity of cerulein‑induced acute pancreatitis by inhibiting p38 activation in mice.
Acute pancreatitis (AP) is an inflammatory disease of the pancreas. Icariin (ICA), a flavonoid glycoside, has been reported to have several pharmacological effects; however, the anti‑inflammatory effects of ICA against AP require further study. Therefore, we aimed to investigate the effect of ICA on cerulein‑induced AP. In the present study, AP was induced by intraperitoneally administering a supramaximal concentration of cerulein (50 µg/kg/h) for 6 h. ICA was also administered intraperitoneally, and mice were sacrificed 6 h after the final cerulein injection. Blood samples were collected to determine serum amylase and lipase levels. The pancreas and lung were rapidly removed for histological examination, and the analysis of myeloperoxidase activity. In addition, reverse transcription‑quantitative polymerase chain reaction was conducted to analyze the expression of inflammatory cytokines in pancreatic tissues. Our results revealed that the administration of ICA prevented an increase in the pancreas weight/body weight ratio of mice and serum digestive enzyme levels. ICA treatment also inhibited cerulein‑induced histological injury and neutrophil infiltration of the pancreas and lung. In addition, ICA suppressed the production of pro‑inflammatory cytokines, including interleukin (IL)‑1β, IL‑6 and tumor necrosis factor‑α in the pancreas. Furthermore, ICA administration was observed to inhibit p38 activation during cerulein‑induced AP. Inhibition of p38 activation resulted in alleviated pancreatitis. Collectively, our results suggested that ICA exhibits anti‑inflammatory effects in cerulein‑induced AP via the inhibition of p38.


Electronic nicotine delivery systems exhibit reduced bronchial epithelial cells toxicity compared to cigarette: the Replica Project.
Electronic nicotine delivery systems (ENDS) may reduce health risks associated with chronic exposure to smoke and their potential benefits have been the matter of intense scientific debate. We aimed to replicate three published studies on cytotoxic and inflammatory effects of cigarette smoke and ENDS aerosol in an independent multi-center ring study. We aimed to establish the reliability of results and the robustness of conclusions by replicating the authors' experimental protocols and further validating them with different techniques. Human bronchial epithelial cells (NCI-H292) were exposed to cigarette whole smoke and vapor phase and to aerosol from ENDS. We also assessed the inflammatory cytokines interleukin-6 and interleukin-8 and the remodeling mediator matrix metalloproteinase-1. We replicated cell viability results and confirmed that almost 80% of cytotoxic effects are due to volatile compounds in the vapor phase of smoke. Our findings substantiated the reduced cytotoxic effects of ENDS aerosol. However, our data on inflammatory and remodeling activity triggered by smoke differed significantly from those in the original reports. Taken together, independent data from multiple laboratories clearly demonstrated the reduced toxicity of ENDS products compared to cigarettes.