Predicting mycotoxins in foods: a review.
The need to ensure the microbiological quality and safety of food products has stimulated interest in the use of mathematical models for quantifying and predicting microbial behaviour. For 20 years, predictive microbiology has been developed for predicting the occurrence of food-borne pathogens, although these tools are dedicated to bacteria. Recently, the situation has changed and a growing number of studies are available in the literature dealing with the predictive modelling approach of fungi. To our knowledge the present one is the first review focussed on predictive mycology and food safety, including mycotoxins; existing kinetic and probability models applied to mycotoxigenic fungi germination and growth, and mycotoxin production are reviewed.


The environment of axonal migration in the developing chick retina: a scanning electron microscopic (SEM) study.
We have made a SEM study of the basal intercellular spaces of the retina in chick embryos of different developmental stages. Since this is the environment where optic axons grow, the structural characteristics of this region might play some role in the orientation of axonal migration towards the choroid fissure. The basal region of undifferentiated retinas is formed by the vitreal expansions of neuroepithelial cells. In pre-axonal stages, the intercellular spaces between these expansions do not show any preferential orientation towards the fissure. The growth cones of ganglion cell axons appear in an apicobasal direction and turn towards the fissure immediately beneath the vitreal surface. Fasciculation is an early event during development and, in the more advanced stages, the vitreal expansions from retinal cells are placed in rows following the same orientation as the axon bundles. These observations are discussed in relationship to current hypotheses on axonal migration and orientation.


Molecular characterisation of mouse and human TSSC6: evidence that TSSC6 is a genuine member of the tetraspanin superfamily and is expressed specifically in haematopoietic organs.
Previous analyses of the murine and human TSSC6 (also known as Phemx) proteins were not carried out using the full length sequence. Using 5'-RACE and cDNA library screening, we identified an additional 5' sequence for both the murine Tssc6 cDNA and its human homologue TSSC6. This novel sequence encodes a 5' exon encoding an in frame, upstream start codon, an N-terminal cytoplasmic domain and a transmembrane domain. The deduced, and now full length, murine and human TSSC6 proteins contained four hydrophobic regions together with other features characteristic of the tetraspanin superfamily. Computational analyses of the full length sequences show that TSSC6 is a genuine, albeit relatively divergent member of this superfamily. Using RNA from a number of mouse tissues, we identified seven splice variants of Tssc6. Splice variants of the human gene were also detected. Tssc6 expression was detected early in embryogenesis in primitive blood cells and was confined to haematopoietic organs in the adult mouse. Tssc6 expression was detected in many haematopoietic cell lines and was highest in cell lines of the erythroid lineage.


Photoinduced formation and characterization of electron-hole pairs in azaxanthylium-derivatized short single-walled carbon nanotubes.
2-Azaxanthone, a nitrogenated derivative of the well-studied organic chromophore xanthone, has been covalently bound through 2-(ethylthio)ethylamido linkers to the carboxylic acid groups of short, soluble single-walled carbon nanotubes (CNTs) of 450 nm average length, and the resulting azaxanthylium-functionalized CNTs (AZX-CNT, 8.5 wt % AZX content) characterized by solution (1)H NMR, Raman and IR spectroscopy and thermogravimetric analysis. Comparison of the quenching of the triplet excited state of AZX (steady-state and time-resolved) and of the transient optical spectra of CNTs and AZX-CNT shows that the covalent linkage boosts the interaction between the azaxanthylium moiety and the short CNT units. The triplet excited state of the azaxanthylium derivative is quenched by CNT with and without covalent bonding, but when it is covalently bonded, the singular transient spectrum is compatible with the photogeneration of electron holes through electron transfer from CNT to excited azaxanthylium units.


Hormone Therapy: A Potential Risk Factor Affecting Survival and Functional Restoration of Transplanted Lymph Nodes.
Background: Transplantation of lymph nodes (LNs) is an increasingly popular option for treating lymphedema. Increasing evidence indicates an intrinsic correlation between estrogen signaling and the lymphatic system. We explored the effects of 17β estradiol and antiestrogen treatment (tamoxifen) on the survival and functional restoration of transplanted popliteal lymph nodes (PLNs). Methods: A total of forty-eight ovariectomized mice were divided into three groups of 16: OVX + E2 (treated with 17β-estradiol), OVX + TMX (treated with tamoxifen), and OVX (control; treated with olive oil as a solvent). After 2 weeks, PLNs were transplanted. Then, reconnections of lymphatic vessels were observed, and the morphology and survival of transplanted PLNs were evaluated 4 weeks after transplantation. T cells, B cells, lymphatic vessels, and high endothelial venules (HEVs) were subjected to immunofluorescence staining or immunohistochemical staining and quantified. Results: The percentage of lymphatic reconnections was 93.75% in the OVX + E2 group, 68.75% in the OVX + TMX group, and 75% in the OVX group. Surviving PLNs were observed in 16 of 16 in the OVX + E2 group, seven of 16 in the OVX + TMX group, and 13 of 16 in the OVX group. The mean size of PLNs in the largest cross section of the OVX + TMX group was significantly lower than that in the other groups. The distributions of B cells and T cells in surviving PLNs were similar to those in normal LNs. The ratio of dilated HEVs/total HEVs and density of lymphatic vessels in the OVX + E2 group were the highest among the three groups, whereas the lowest ratio and density were observed in the OVX + TMX group. Conclusion: Tamoxifen treatment might lead to cellular loss of transplanted LNs and interfere with the structural reconstruction and functional restoration, thereby inhibiting the survival of transplanted PLNs. Estrogen treatment facilitated the maintenance and regeneration of functional HEVs as well as lymphangiogenesis.


A Survey of Commercially Available Isomaltooligosaccharide-Based Food Ingredients.
Isomaltooligosaccharides (IMOs) are included in many commercially available food products including protein/fiber bars, shakes, and other dietary supplements. Marketed as "high fiber," "prebiotic soluble fiber," and/or as a "low-calorie, low glycemic sweetener," IMO may be present in significant amounts, for example, more than 15 g/item or serving. Herein, high-pressure anion exchange chromatography with pulsed amperometric detection and high-pressure liquid chromatography with differential refractive index detection are used to compare 7 commercially available IMO-containing bulk food ingredients. The ingredients are typical of those produced either (a) via bacterial fermentation ("fermented" IMO or MIMO) of sucrose in the presence of a maltose acceptor mediated by a glucosyltransferase enzyme (dextransucrase), or (b) via transglycosylation of hydrolyzed starch with α-glucosidase ("industrial" IMO). Analysis of the results with respect to digestibility suggests that the potential glycemic impact of the ingredients and products containing "industrial" IMO may be inconsistent with the product labeling and/or certificates of analysis with respect to overall fiber content, prebiotic fiber content, and glycemic response and are thus inappropriate for diabetic patients and those on low-carbohydrate (for example, ketogenic) diets.


Reducing bacterial counts in dental unit waterlines: distilled water vs. antimicrobial agents.
This study evaluated five chemical disinfectants to compare their abilities to improve dental unit waterline quality and assess their effects, if any, on the biofilm layer. Sixty new dental units, with a closed-circuit water system, were used to compare microbial levels in DUWLs treated with five antimicrobials: Listerine, Bio 2000, Rembrandt, Dentosept, and sodium fluoride to a control group of sterile distilled water alone over a six-week period. For all units, the waterlines were filled with solution, left overnight, and then flushed for 30 seconds with sterile distilled water the following morning prior to patient treatment. Waterlines were examined for biofilm buildup using scanning electron microscopy and colony-forming-unit counts. The sodium fluoride and the four chemical antimicrobials reduced the microbial count to 200 cfu/ml or less. Only samples taken from dental units receiving the control treatment (distilled water with no added antimicrobial) failed to meet ADA's stated goal. Examination of the SEMs revealed an apparent decrease in the biofilm mass but not elimination, despite repeated treatment with the four antimicrobial materials. Even in a closed-circuit water system, distilled water alone cannot reduce microbial contamination of dental treatment water from dental unit waterlines to the 200 cfu/ml ADA stated goal. However, water treated with Listerine mouthrinse, Rembrandt mouthrinse, Bio 2000, 0.5 percent sodium fluoride and Dentosept, did meet the microbial reduction goal. The biofilm apparently was reduced in volume, but not entirely eliminated. The ADA goal of a maximum of 200 cfu/ml was achieved using any of five chemical antimicrobials and distilled water in a closed-water system. Despite the successful reduction in microbial contamination of the dental treatment water, the biofilm was not completely eliminated. Biofilm elimination and prevention would be needed through some other means.


Role of a wireless surface electromyography in dystonic gait in functional movement disorders: A case report.
Dystonic gait (DG) is one of clinical symptoms associated with functional dystonia in the functional movement disorders (FMDs). Dystonia is often initiated or worsened by voluntary action and associated with overflow muscle activation. There is no report for DG in FMDs caused by an abnormal pattern in the ankle muscle recruitment strategy during gait. A 52-year-old male patient presented with persistent limping gait. When we requested him to do dorsiflexion and plantar flexion of his ankle in the standing and seating positions, we didn't see any abnormality. However, we could see the DG during the gait. There were no evidences of common peroneal neuropathy and L5 radiculopathy in the electrodiagnostic study. Magnetic resonance imaging of the lumbar spine, lower leg, and brain had no definite finding. No specific finding was seen in the neurologic examination. For further evaluation, a wireless surface electromyography (EMG) was performed. During the gait, EMG amplitude of left medial and lateral gastrocnemius (GCM) muscles was larger than right medial and lateral GCM muscles. When we analyzed EMG signals for each muscle, there were EMG bursts of double-contraction in the left medial and lateral GCM muscles, while EMG analysis of right medial and lateral GCM muscles noted regular bursts of single contraction. We could find a cause of DG in FMDs. We report an importance of a wireless surface EMG, in which other examination didn't reveal the cause of DG in FMDs.


Redescriptions, new synonymy, new combination and new records of Bacis Dejean, 1836 and Oligocorynus Dejean, 1876 (Coleoptera: Erotylidae: Erotylinae) for Colombia.
Bacis nigropictus Crotch, 1876 and Phricobacis flavomaculatus Mader, 1943 are redescribed. Redescriptions are provided with illustrations of diagnostic characters. Based upon the study of type material, Zonarius limbatus Kuhnt, 1910 is considered a new synonym of B. nigropictus. A lectotype is designated for Zonarius limbatus Kuhnt, 1910. Based on character analyses, Phricobacis flavomaculatus is here transferred to the genus Oligocorynus Dejean, 1836, becoming Oligocorynus flavomaculatus (Mader), new combination. Bacis nigropictus is newly listed for Colombia and O. flavomaculatus is considered new country record from Colombia.


Clustering asian and north african countries according to trend of colon and rectum cancer mortality rates: an application of growth mixture models.
Colorectal cancer is the second most common cause of cancer death with half a million deaths per year. Incidence and mortality rates have demonstrated notable changes in Asian and African countries during the last few decades. In this study, we first aimed to determine the trend of colorectal cancer mortality rate in each Institute for Health Metrics and Evaluation (IHME) region, and then re-classify them to find more homogenous classes. Our study population consisted of 52 countries of Asia and North Africa in six IHME pre-defined regions for both genders and age-standardized groups from 1990 to 2010.We first applied simple growth models for pre-defined IHME regions to estimate the intercepts and slopes of mortality rate trends. Then, we clustered the 52 described countries using the latent growth mixture modeling approach for classifying them based on their colorectal mortality rates over time. Statistical analysis revealed that males and people in high income Asia pacific and East Asia countries were at greater risk of death from colon and rectum cancer. In addition, South Asia region had the lowest rates of mortality due to this cancer. Simple growth modeling showed that majority of IHME regions had decreasing trend in mortality rate of colorectal cancer. However, re-classification these countries based on their mortality trend using the latent growth mixture model resulted in more homogeneous classes according to colorectal mortality trend. In general, our statistical analyses showed that most Asian and North African countries had upward trend in their colorectal cancer mortality. We therefore urge the health policy makers in these countries to evaluate the causes of growing mortality and study the interventional programs of successful countries in managing the consequences of this cancer.


Recurrent cytogenetic aberrations and loss of constitutional heterozygosity in ovarian carcinomas.
Cancer is regarded as the result of the accumulation of multiple genetic changes leading to either the activation of oncogenes and increased expression of mitogenic pathways or the inactivation of tumor suppressor genes. It was our interest to investigate malignant ovarian tumors with cytogenetic and molecular techniques to evaluate their consistent genetic alterations. Cytogenetic analysis was performed on 30 short-term cultured ovarian carcinomas. Fifteen tumors revealed clonal cytogenetic abnormalities, 10 of which had very complex karyotypes. The most consistent finding was a 19p+ marker chromosome which was present in half of the cytogenetically abnormal tumors with complex chromosome aberrations. Four tumors showed structural rearrangements resulting in loss of 11p13-pter material. Parallel DNA extracts from 18 tumor samples and corresponding normal white blood cells were analyzed by Southern blotting using 4 polymorphic probes spanning the region 11p15.1 to 11p15.5 and one polymorphic probe mapped to 19p13. Regarding the 11p probes, reduction to homozygosity in the tumor DNA was found in 9 of 17 informative cases. Loss of 19p alleles was found in 5 of 13 informative tumors. Our findings suggest that tumor suppressor genes located on the short arms of chromosomes 11 and 19 are involved in the development of human ovarian cancer.


Orthogonally functionalized naphthodithiophenes: selective protection and borylation.
Selective functionalization protocols of naphtho[1,2-b;5,6-b']dithiophene (NDT3) by combining protection of the thiophene α-positions and direct borylation on the naphthalene core are described, which allows synthesizing a number of new NDT3-based building blocks with various substituents and isomeric NDT3-based polymers with different main chain structures. The same protocol is applicable to other isomeric naphthodithiophenes (NDTs), which affords a set of key building blocks for the development of elaborated functional π-materials.


Advancing regenerative surgery in orthopaedic sports medicine: the critical role of the surgeon.
The constant desire to improve outcomes in orthopaedic sports medicine requires us to continuously consider the challenges faced in the surgical repair or reconstruction of soft tissue and cartilaginous injury. In many cases, surgical efforts targeted at restoring normal anatomy and functional status are ultimately impaired by the biological aspect of the natural history of these injuries, which acts as an obstacle to a satisfactory repair process after surgery. The clinical management of sports injuries and the delivery of appropriate surgical intervention are continuously evolving, and it is likely that the principles of regenerative medicine will have an increasing effect in this specialized field of orthopaedic practice going forward. Ongoing advances in arthroscopy and related surgical techniques should facilitate this process. In contrast to the concept of engineered replacement of entire tissues, it is probable that the earliest effect of regenerative strategies seen in clinical practice will involve biological augmentation of current operative techniques via a synergistic process that might be best considered "regenerative surgery." This article provides an overview of the principles of regenerative surgery in cartilage repair and related areas of orthopaedic surgery sports medicine. The possibilities and challenges of a gradual yet potential paradigm shift in treatment through the increased use of biological augmentation are considered. The translational process and critical role to be played by the specialist surgeon are also addressed. We conclude that increased understanding of the potential and challenges of regenerative surgery should allow those specializing in orthopaedic surgery sports medicine to lead the way in advancing the frontiers of biological strategies to enhance modern clinical care in an evidence-based manner.


[A spontaneously resolving T-cell lymphoma].
Primary cutaneous CD30+ anaplastic large-cell lymphoma is a rare form of non-Hodgkin's lymphoma, which is restricted to the skin. A 50-year-old man presented with an asymptomatic tumorous area in the groin that had appeared within the previous week, and a longer history of a transient red, flaking area in the popliteal space. Histopathological findings were consistent with CD30+ anaplastic large-cell lymphoma. Staging demonstrated no extracutanous spread. The skin lesions disappeared without treatment within 3 months. Primary cutaneous CD30+ anaplastic large-cell lymphoma is a rare condition. It has a histopathological picture of a diffuse proliferation of large atypical anaplastic cells, suggesting an unfavourable disease course. However, this condition is characterised by a indolent course and favourable prognosis since spontaneous complete regression can occur.


Streaming Potential with Ideally Polarizable Electron-Conducting Substrates.
With nonconducting substrates, streaming potential in sufficiently broad (vs Debye screening length) capillaries is well known to be a linear function of applied pressure (and coordinate along the capillary). This study for the first time explores streaming potential with ideally polarizable electron-conducting substrates and shows it to be a nonlinear function of both coordinate and applied pressure. Experimental manifestations can be primarily expected for streaming potentials arising along thin porous electron-conducting films experiencing solvent evaporation from the film side surface. Model predictions are in good qualitative agreement with literature experimental data.


Strict conservation of the ITS regions of the ribosomal RNA genes in Atlantic cod (Gadus morhua L.).
The nucleotide sequence of the internal transcribed region (ITS) of ribosomal RNA genes from Atlantic cod (Gadus morhua L.) was determined. The complete ITS region spanned approximately 1113 base pairs. The ITS1 region comprised 532 base pairs, the 5.8S region 159, and the ITS2 region contained 422 base pairs. Sequence data were obtained from a total of 12 samples, one pool from six cod and 11 individuals. The sequencing was carried out in two separate experimental periods employing slightly different methodology. The samples were from two different cod stocks, Norwegian costal cod and North East Arctic cod. The sequence analysis showed that in the 12 samples, the ITS region, including the 5.8S RNA, was identical. The ITS region is thus totally conserved in these two cod stocks. The extreme conservation of the ITS regions in the cod rDNA could reflect the small genome size of cod and/or indicate a specific critical role in the processing of the ribosomal units in cold-adapted species.


Regeneration and reprogramming compared.
Dedifferentiation occurs naturally in mature cell types during epimorphic regeneration in fish and some amphibians. Dedifferentiation also occurs in the induction of pluripotent stem cells when a set of transcription factors (Oct4, Sox2, Klf4 and c-Myc) is over expressed in mature cell types. We hypothesised that there are parallels between dedifferentiation or reprogramming of somatic cells to induced pluripotent stem cells and the natural process of dedifferentiation during epimorphic regeneration. We analysed expression levels of the most commonly used pluripotency associated factors in regenerating and non-regenerating tissue and compared them with levels in a pluripotent reference cell. We found that some of the pluripotency associated factors (oct4/pou5f1, sox2, c-myc, klf4, tert, sall4, zic3, dppa2/4 and fut1, a homologue of ssea1) were expressed before and during regeneration and that at least two of these factors (oct4, sox2) were also required for normal fin regeneration in the zebrafish. However these factors were not upregulated during regeneration as would be expected if blastema cells acquired pluripotency. By comparing cells from the regeneration blastema with embryonic pluripotent reference cells we found that induced pluripotent stem and blastema cells do not share pluripotency. However, during blastema formation some of the key reprogramming factors are both expressed and are also required for regeneration to take place. We therefore propose a link between partially reprogrammed induced pluripotent stem cells and the half way state of blastema cells and suggest that a common mechanism might be regulating these two processes.


Proinsulin C-peptide regulates ribosomal RNA expression.
Proinsulin C-peptide is internalized into cells, but a function of its intracellular localization has not been established. We now demonstrate that, upon cellular entry, C-peptide is localized to the nucleoli, where it promotes transcription of genes encoding for ribosomal RNA. We find that C-peptide binds to histones and enhances acetylation of lysine residue 16 of histone H4 at the promoter region of genes for ribosomal RNA. In agreement with synchrony of ribosomal RNA synthesis and cell proliferation, we show that C-peptide stimulates proliferation in chondrocytes and HEK-293 cells. This regulation of ribosomal RNA provides a mechanism by which C-peptide can exert transcriptional effects and implies that the peptide has growth factor activity.


Experimental remarks after cervical sympathectomy.
The present experimental work was undertaken to determine some quantitative changes occurring after cervical sympathectomy applied for the treatment of Raynaud's diseases. The blood flow in the brachial artery was measured before and after sympathectomy as well as the temperature, haemoglobin concentration and oxyhaemoglobin saturation in arterial and venous blood, pH and PCO2 of the arterial blood.


Mechanism of DNA damage by cadmium and interplay of antioxidant enzymes and agents.
Cadmium is an environmental toxicant, which causes cancer in different organs. It was found that it damages DNA in the various tissues and cultured cell lines. To investigate the mechanism of DNA damage, we have studied the effect of cadmium-induced DNA damage in plasmid pBR322 DNA, and the possible ameliorative effects of antioxidative agents under in vitro conditions. It was observed that cadmium alone did not cause DNA damage. However, it caused DNA damage in the presence of hydrogen peroxide, in a dose dependent manner, because of production of hydroxyl radicals. Findings from this study show the conversion of covalently closed circular double-stranded pBR 322 DNA to the open circular and linear forms of DNA when treated with 10 muM cadmium and various concentrations of H(2)O(2). The conversion was due to nicking in DNA strands. The observed rate of DNA strand breakage was dependent on H(2)O(2) concentration, temperature, and time. Metallothionein I failed to prevent cadmium-induced DNA nicking in the presence of H(2)O(2). Of the two antioxidant enzymes (catalase and superoxide dismutase) studied, only catalase conferred significant (50-60%) protection. EDTA and DMSO exhibited protection similar to catalase, while mannitol showed only about 20% protection against DNA damage. Ethyl alcohol failed to ameliorate cadmium-induced DNA strands break. From this study, it is plausible to infer that cadmium in the presence of hydrogen peroxide causes DNA damage probably by the formation of hydroxyl ions. These results may indicate that cadmium in vivo could play a major role in the DNA damage induced by oxidative stress.


Vitamin D Screening and Supplementation in Community-Dwelling Adults: Common Questions and Answers.
Measurement of vitamin D levels and supplementation with oral vitamin D have become commonplace, although clinical trials have not demonstrated health benefits. The usefulness of serum 25-hydroxyvitamin D levels to assess adequate exposure to vitamin D is hampered by variations in measurement technique and precision. Serum levels less than 12 ng per mL reflect inadequate vitamin D intake for bone health. Levels greater than 20 ng per mL are adequate for 97.5% of the population. Routine vitamin D supplementation does not prolong life, decrease the incidence of cancer or cardiovascular disease, or decrease fracture rates. Screening asymptomatic individuals for vitamin D deficiency and treating those considered to be deficient do not reduce the risk of cancer, type 2 diabetes mellitus, or death in community-dwelling adults, or fractures in persons not at high risk of fractures. Randomized controlled trials of vitamin D supplementation in the treatment of depression, fatigue, osteoarthritis, and chronic pain show no benefit, even in persons with low levels at baseline.


The Dual Role of Bone Morphogenetic Proteins in Cancer.
Bone morphogenetic proteins (BMPs) are a diverse class of molecules with over 20 growth factor proteins that belong to the transforming growth factor-β (TGF-β) family and are highly associated with bone formation and disease development. Aberrant expression of various BMPs has been reported in several cancer tissues. Biological function studies have elicited the dual role of BMPs in both cancer development and suppression. Furthermore, a variety of BMP antagonists, ligands, and receptors have been shown to reduce or enhance tumorigenesis and metastasis. Knockout mouse models of BMP signaling components have also revealed that the suppression of BMP signaling impairs cancer metastasis. Herein, we highlight the basic clinical background and involvement of BMPs in modulating cancer progression and their dynamic interactions (e.g., with microRNAs) in the tumor microenvironment in addition to their mutations and roles in chemoprevention. We also suggest that BMPs should be considered a powerful putative therapeutic target in tumorigenesis and bone metastasis.


Circulating extracellular vesicles as new inflammation marker in HIV infection.
Extracellular vesicles, released by cell pullulation, are surrounded by a phospholipid bilayer and carry proteins as well and genetic material. It has been shown that extracellular vesicles mediate intercellular communication in several conditions, such as inflammation, immunodeficiency, tumor growth, and viral infections. Here, we analyzed circulating levels of extracellular vesicles in order to clarify their role in chronic inflammation mechanisms characterizing HIV patients. We analyzed and subtyped circulating levels of extracellular vesicles, through a recently developed flow cytometry method. In detail, endothelial-derived extracellular vesicles (CD31+/CD41a-/CD45-, EMVs), extracellular vesicles stemming from leukocytes (CD45+, LMVs) and platelets (CD41a+/CD31+) were identified and enumerated. Moreover, we analyzed the extracellular vesicle protein cargo with proteomic analysis. Circulating levels of total extracellular vesicles, EMVs and LMVs were significantly lower in the HIV+ patients than in healthy subjects, whereas platelet-derived extracellular vesicles resulted higher in patients than in the healthy population. Proteomic analysis showed the upregulation of gammaIFN and IL1α, and down-regulation of OSM, NF-kB, LIF, and RXRA signaling resulted activated in this patients. These data demonstrate, for the first time that HIV infection induces the production of extracellular vesicles containing mediators that possibly feed the chronic inflammation and the viral replication. These two effects are connected as the inflammation itself induces the viral replication. We, therefore, hypothesize that HIV infection inhibits the production of extracellular vesicles that carry anti-inflammatory molecules.


Stereospecific reduction of phosphine oxides to phosphines by the use of a methylation reagent and lithium aluminum hydride.
[figure: see text] Various phosphine oxides are efficiently reduced by the use of a methylation reagent and lithium aluminum hydride. Optically active P-chirogenic phosphine oxides are also reduced with inversion of configuration at phosphorus atom by treatment with methyl triflate, followed by reaction with LiAlH4.


Prevalence of HCV resistance-associated substitutions among treatment-failure patients receiving direct-acting antiviral agents.
Direct-acting antiviral (DAA) failure, which is mainly associated with the selection of resistance-associated substitutions (RASs), is not rare in HCV treatment. RAS data collected from published literature and RAS prevalence were integrated using meta-analysis. DAA-failure-associated RASs were identified by comparing their prevalence between DAA-failure and DAA-naïve patients. Prevalences of emerging RASs that occurred during treatment were also estimated. A total of 2932 DAA-naïve patients and 1466 DAA-failure patients were included. Significant differences in the prevalence of RASs were found in 76 scenarios that involved 34 RASs (11 in NS3, 18 in NS5A and 5 in NS5B), 4 genotypes (GTs) (GT1a, GT1b and GT3-4) and 14 DAAs (6 NS3 protease inhibitors [PIs], 6 NS5A inhibitors and 2 NS5B inhibitors). For NS3, the DAA-failure-associated RASs included V36L, Y56H, Q80K/R, R155K, A156T and D168A/E/L/T/V/Y. Substitutions at R155 and D168 were dominant for most NS3 PIs. For NS5A, DAA-failure-associated RASs included K24R, Q30R, L31M, and P32L in GT1a; R30Q/H, L31F/I/M/V, P58S, and Y93H in GT1b; A30K, L31M and Y93H in GT3; and M31V and Y93H in GT4. Y93H was the most prevalent RAS for NS5A inhibitors. DAA-failure-associated RASs were found at only five positions in NS5B. The majority of DAA-failure patients relapsed. A significant difference was detected for only four RAS sites between relapse patients and nonresponse/breakthrough patients. The RAS prevalence in DAA-failure patients varied among the HCV GTs and DAA regimens. The identified treatment-selected resistance patterns for broadly used DAA regimens will enable the selection of optimized retreatment options.


Single-molecule probing of adsorption and diffusion on silica surfaces.
Single-molecule spectroscopy has emerged as a valuable tool in probing kinetics and dynamic equilibria in adsorption because advances in instrumentation and technology have enabled researchers to obtain high signal-to-noise ratios for common dyes at room temperature. Single-molecule spectroscopy was applied to the study of an important problem in chromatography: peak broadening and asymmetry in the chromatograms of pharmaceuticals, peptides, and proteins. Using DiI, a cationic dye that exhibits the same problematic chromatographic behavior, investigators showed that the adsorption sites that cause chromatographic problems are located at defects on the silica crystal surface.


Renal denervation: results of a single-center cohort study.
To investigate the effect of renal denervation on office-based and 24-h ambulatory blood pressure measurements (ABPM) in a highly selective patient population with drug-resistant hypertension. Patients with drug resistant hypertension eligible for renal denervation were included in the study population. Office blood pressure and ABPM were assessed prior to and after renal denervation. To detect procedure related renal or renal artery damage, magnetic resonance imaging (MRI) and angiography (MRA) were performed pre-interventional, one day post-interventional, and one month after renal denervation. Mean follow-up time between renal denervation and blood pressure re-assessment was 9.5 ± 3.9 months. Between August 2011 and March 2013, 17 patients prospectively underwent renal denervation. Pre-interventional mean office blood pressure and ABPM were 177.3 ± 20.3/103.8 ± 20.4 mmHg and 155.2 ± 20.5/93.7 ± 14.5 mmHg, respectively. Post-interventional, office blood pressure was significantly reduced to 144.7 ± 14.9/89.5 ± 12.1 (p < 0.05). ABPM values remained unchanged (147.9 ± 20.3/90.3 ± 15.6, p > 0.05). The number of prescribed antihypertensive drugs was unchanged after renal denervation (4.7 ± 2.0 vs. 4.2 ± 1.2, p = 0.18). No renovascular complications were detected in follow-up MRI. After renal denervation, no significant decrease in ABPM was observed. These results may indicate a limited impact of renal denervation for drug resistant hypertension. • Renal denervation showed no significant effects on 24-h ambulatory blood pressure measurements. • A significant decrease in office blood pressure measurements may be explained by a potential detection bias. • Renal artery alterations were not observed on follow-up MRI scans.


The Activity of Ten Natural Extracts Combined in a Unique Blend to Maintain Cholesterol Homeostasis-In Vitro Model.
Hypercholesterolemia is a major cause of cardiovascular disease and statins, the HMGCoA inhibitors, are the most prescribed drugs. Statins reduce the production of hepatic cholesterol, leading to greater expression of the LDL receptor and greater absorption of circulating LDL, reducing peripheral LDL levels. Unfortunately, statins are believed to induce myopathy and other severe diseases. To overcome this problem, safe nutraceuticals with the same activity as statins could hold great promise in the prevention and treatment of hypercholesterolemia. In this study, the anti-cholesterol efficacy of a new nutraceutical, called Esterol10®, was evaluated. HepG2 cells were used to study the biological mechanisms exerted by Esterol10® analyzing different processes involved in cholesterol metabolism, also comparing data with Atorvastatin. Our results indicate that Esterol10® leads to a reduction in total hepatocyte cholesterol and an improvement in the biosynthesis of free cholesterol and bile acids. Furthermore, the anti-cholesterol activity of Esterol10® was also confirmed by the modulation of the LDL receptor and by the accumulation of lipids, as well as by the main intracellular pathways involved in the metabolism of cholesterol. Esterol10® is safe and effective with anti-cholesterol activity, potentially providing an alternative therapy to those based on statins for hypercholesterolemia disease.


Reforming hospital nursing: the experiences of Maria Machin.
The reform of hospital nursing in the last quarter of the nineteenth century brought nursing leaders into conflict with the gendered and class bound structure of Victorian society. The experiences of Maria Machin are used in this article as an example of the barriers nursing leaders had to overcome in order to establish a competent nursing service. While Machin was eminently successful in improving patient care and expanding the knowledge base of her nurses, she could not change the perceptions of nursing which the public at large held. At the beginning of the nineteenth century hospital nurses had been essentially cleaning women who gave some of the less important nursing care. They formed a cheap service which many hospital governors considered a relatively low priority in the overall operation of the hospital. This view of nursing persisted long after the reformers had made nursing into something quite different. Machin's nursing career also illustrates how nursing participated in a major aspect of British imperialism, the export of professional expertise and administrative skills as well as the way nursing fitted into the rise of the new professionalism.


Renewable bio-based adhesive fabricated from a novel biopolymer and soy protein.
In this study, a bio-based soy protein adhesive derived from environmentally friendly and renewable enzymatic hydrolysis lignin (EHL), epoxidized soybean oil (ESO), and soy protein isolate (SPI), was successfully prepared. A novel biopolymer (EHL-ESO), as a multifunctional crosslinker, was firstly synthesized from modified EHL and ESO, and then crosslinked with soy protein isolate to obtain a bio-based soy protein adhesive. The structure, thermal properties, and adhesion performance of the obtained soy protein adhesives were determined by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM) and wet shear strength. The maximum degradation temperature of SPI/EHL-ESO adhesives (332-343 °C) was higher than that of the pristine SPI adhesive (302 °C). Moreover, plywood bonded by the modified adhesive reached a maximum wet shear strength value of 1.07 MPa, a significant increase of 101.8% from the plywood bonded by pristine SPI adhesive. The enhancements in the thermal stability and wet shear strength were attributed to the formation of a dense crosslinking network structure. This work not only highlights the potential to replace petroleum-based polymers, but also presents a green approach to fabricate fully bio-based soy protein adhesive for preparing all-biomass wood composite materials.


Implementation and outcomes of guideline revisions for the prevention of mother-to-child HIV transmission in Mother Support Programme, Addis Ababa, Ethiopia.
About 40% of the new HIV infections in Ethiopia are among children < 15 years of age. The great majority of these infections occur through Mother-to-child HIV transmission (MTCT). For prevention of MTCT, the national guidelines has been revised to incorporate scientific advances in HIV prevention, treatment and care. Since 2005, the country has been implementing a peer mentor programme called Mother Support Group (MSG), which provides psychosocial and adherence support for HIV positive mothers. This study examined implementation of PMTCT guidelines revisions and outcomes of HIV exposed babies in the MSG in Addis Ababa. Retrospective routine data were collected between 2005 and August 2013 from seven randomly selected primary health facilities. Odds ratios and 95% confidence intervals were calculated using logistic regression models. Several guidelines revisions were made between 2001 and 2013 in HIV testing approaches, prophylactic antiretroviral options, infant feeding recommendations and infant HIV testing algorithms. Revisions on the CD4 thresholds were associated with a significant increase in the proportion of women initiating antiretroviral treatment from 0 in 2005 to 62% in 2013. Revisions in infant feeding recommendations led to a 92.3% reported practice of exclusive breastfeeding in 2013 compared to 60.9% in 2005. Two and four percent of the HIV exposed babies were HIV positive by six and 18 months respectively. Not receiving prophylactic ART and receiving mixed feeding were independent predictors for babies having an HIV positive antibody test at 18 months. The rate of HIV status disclosure increased significantly year by year. Over the years, the PMTCT recommendations have moved from having a solo focus on PMTCT to holistic and inclusive approaches emphasizing survival beyond HIV prevention. The data reflect favourable outcomes of HIV exposed babies in terms of averted MTCT though serious gaps in data quality remain. For successful implementation of Option-B plus, the identified gaps in the MSG need to be addressed.


Immunomodulatory Therapy and an Insidious Presentation of a Large Intra-Abdominal Abscess.
Crohn's disease is a disorder characterized by transmural inflammation which can potentially affect any part of the gastrointestinal tract from the mouth to the perianal area. Cohn's disease is a systemic disease characterized by a relapsing remitting course, with variable intestinal and extra-intestinal complications. Abdominal and pelvic abscesses are not an uncommon complication of Crohn's disease occurring in 10-30 percent of all patients. We present the case of a 21-year-old male with Crohn's disease presenting with a massive abdominal abscess, whose diagnosis was delayed given lack of typical symptoms. Shortly after initiating therapy with Prednisone and Adalimumab he presented with worsening abdominal distention. Cross sectional imaging of the abdomen with IV contrast (Figure 1) demonstrated a 34cm x 23 cm x 11 cm rim-enhancing fluid collections in the abdomen and pelvis consistent with a large intra-abdominal abscess. He underwent an exploratory laparotomy, abdominal washout, and wound vacuum placement. Five liters of purulent fluid were aspirated and cultures grew citrobacter, veillonella and candida glabrata. A bowel perforation was suspected as the etiology for abscess formation; however magnetic resonance heterography (Figure2) was unremarkable. He was treated with appropriate antibiotics, antifungal agents, and was started on Aprisa. His course was complicated with recurrence of intra-abdominal abscesses and a colocutaneous fistula for which he underwent an open sigmoidectomy with a diverting loop colostomy. After condirmation of healing with repeat imaging, he was an uneventful postoperative course. He followed as an outpatient and continues to do well on Infliximab. Most abscesses are picked up in their early stages given characteristic symptoms; however in presence of immunosuppressive therapy the host immune system can be suppressed leading to delayed diagnosis. The presence of a massive intra-abdominal purulent fluid collection of this size has not been described on our review of the literature. Furthermore, despite the abscess taking up most of the abdominal cavity, the fairly limited symptom burden highlights the importance of having high degree of clinical suspicion for infectious compications in Crohn's disease patients even when classical symptoms are not present.


ATP8B1 Deficiency Results in Elevated Mitochondrial Phosphatidylethanolamine Levels and Increased Mitochondrial Oxidative Phosphorylation in Human Hepatoma Cells.
ATP8B1 is a phospholipid flippase that is deficient in patients with progressive familial intrahepatic cholestasis type 1 (PFIC1). PFIC1 patients suffer from severe liver disease but also present with dyslipidemia, including low plasma cholesterol, of yet unknown etiology. Here we show that ATP8B1 knockdown in HepG2 cells leads to a strong increase in the mitochondrial oxidative phosphorylation (OXPHOS) without a change in glycolysis. The enhanced OXPHOS coincides with elevated low-density lipoprotein receptor protein and increased mitochondrial fragmentation and phosphatidylethanolamine levels. Furthermore, expression of phosphatidylethanolamine N-methyltransferase, an enzyme that catalyzes the conversion of mitochondrial-derived phosphatidylethanolamine to phosphatidylcholine, was reduced in ATP8B1 knockdown cells. We conclude that ATP8B1 deficiency results in elevated mitochondrial PE levels that stimulate mitochondrial OXPHOS. The increased OXPHOS leads to elevated LDLR levels, which provides a possible explanation for the reduced plasma cholesterol levels in PFIC1 disease.


Visual awareness and the on-line modification of action.
An influential theory of visually guided action proposes that (a) conscious perception of target displacement disrupts on-line action and (b) small target perturbations are inconsequential, provided the participant is unaware of them. This study examined these claims in a study of rapid aiming movements to targets. Novel features included on-line verbal reports of target displacement, and the factorial combination of small versus large displacements occurring near peak saccadic velocity or 100 ms later. Although awareness of target displacement had no effect on movement kinematics, even small target displacements near peak saccadic velocity affected kinematic measures. These results support both a strong view of visual stream separation in the on-line control of action and richer spatial coding by unconscious processes than has previously been acknowledged.


The Role of N6-Methyladenosine Methylation in the Progression of Endometrial Cancer.
Purpose: N6-methyladenosine (m6A) methylation was the most abundant internal modification on messenger RNAs in eukaryotes. This study intended to explore the role of m6A methylation in endometrial cancer (EC). Materials and Methods: The m6A-sequencing data "GSE93911" of human EC were downloaded from Gene Expression Omnibus database. Hisat2 software and MACS2 were used to perform the alignment of reads and m6A methylation peak calling, and the peaks were annotated using Chipseeker. Then, differential m6A methylation peaks between normal and tumor samples were analyzed, followed by the functional enrichment analysis of the differentially methylated genes in promoter and 3' untranslated region (UTR) using Clusterprofiler. Based on the 450K methylated chip data, gene expression and clinical data in The Cancer Genome Atlas, the differentially methylated genes were verified, followed by Cox univariate/multivariate regression analysis and survival analysis. Finally, a risk prognosis model was constructed. Results: The m6A peak number was decreased in EC. The distribution of m6A peaks was highly enriched near transcriptional start site, in promoter, UTR, intron and exon, followed by distal intergenic. A total of 581 differentially methylated genes (361 hyper- and 220 hypomethylated genes) were identified in promoter and UTR regions that were enriched in insulin resistance (IR) and extracellular matrix (ECM). A total of 181 genes with significant differential expressions and differential methylation site in EC were selected. Of which, 31 genes were correlated with survival, and an 11-gene risk prognosis model was identified, including GDF7, BNC2, SLC8A1, B4GALNT3, DHCR24, ESRP1, HOXB9, IGSF9, KIAA1324, MSnX1, and PHGDH. Conclusion: The m6A methylation regulated EC progression by targeting the genes related to IR and ECM. A 11-gene risk prognosis model was identified to predict survival of patients with EC.


The Host Protein CAD Regulates the Replication of FMDV through the Function of Pyrimidines' De Novo Synthesis.
Foot-and-mouth disease virus (FMDV) is a single-stranded picornavirus that causes economically devastating disease in even-hooved animals. There has been little research on the function of host cells during FMDV infection. We aimed to shed light on key host factors associated with FMDV replication during acute infection. We found that HDAC1 overexpression in host cells induced upregulation of FMDV RNA and protein levels. Activation of the AKT-mammalian target of rapamycin (mTOR) signaling pathway using bpV(HOpic) or SC79 also promoted FMDV replication. Furthermore, short hairpin RNA (shRNA)-induced suppression of carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD), a transcription factor downstream of the AKT-mTOR signaling pathway, resulted in downregulation of FMDV RNA and protein levels. Coimmunoprecipitation assays showed that the ACTase domain of CAD could interact with the FMDV 2C protein, suggesting that the ACTase domain of CAD may be critical in FMDV replication. CAD proteins participate in de novo pyrimidine synthesis. Inhibition of FMDV replication by deletion of the ACTase domain of CAD in host cells could be reversed by supplementation with uracil. These results revealed that the contribution of the CAD ACTase domain to FMDV replication is dependent on de novo pyrimidine synthesis. Our research shows that HDAC1 promotes FMDV replication by regulating de novo pyrimidine synthesis from CAD via the AKT-mTOR signaling pathway. IMPORTANCE Foot-and-mouth disease virus is an animal virus of the Picornaviridae family that seriously harms the development of animal husbandry and foreign trade of related products, and there is still a lack of effective means to control its harm. Replication complexes would generate during FMDV replication to ensure efficient replication cycles. 2C is a common viral protein in the replication complex of Picornaviridae virus, which is thought to be an essential component of membrane rearrangement and viral replication complex formation. The host protein CAD is a key protein in the pyrimidines de novo synthesis. In our research, the interaction of CAD and FMDV 2C was demonstrated in FMDV-infected BHK-21 cells, and it colocalized with 2C in the replication complex. The inhibition of the expression of FMDV 3D protein through interference with CAD and supplementation with exogenous pyrimidines reversed this inhibition, suggesting that FMDV might recruit CAD through the 2C protein to ensure pyrimidine supply during replication. In addition, we also found that FMDV infection decreased the expression of the host protein HDAC1 and ultimately inhibited CAD activity through the AKT-mTOR signaling pathway. These results revealed a unique means of counteracting the virus in BHK-21 cells lacking the interferon (IFN) signaling pathway. In conclusion, our study provides some potential targets for the development of drugs against FMDV.


Capturing the two dimensions of residential segregation at the neighborhood level for health research.
Two conceptual and methodological foundations of segregation studies are that (i) segregation involves more than one group, and (ii) segregation measures need to quantify how different population groups are distributed across space. Therefore, percentage of population belonging to a group is not an appropriate measure of segregation because it does not describe how populations are spread across different areal units or neighborhoods. In principle, evenness and isolation are the two distinct dimensions of segregation that capture the spatial patterns of population groups. To portray people's daily environment more accurately, segregation measures need to account for the spatial relationships between areal units and to reflect the situations at the neighborhood scale. For these reasons, the use of local spatial entropy-based diversity index (SHi ) and local spatial isolation index (Si ) to capture the evenness and isolation dimensions of segregation, respectively, are preferable. However, these two local spatial segregation indexes have rarely been incorporated into health research. Rather ineffective and insufficient segregation measures have been used in previous studies. Hence, this paper empirically demonstrates how the two measures can reflect the two distinct dimensions of segregation at the neighborhood level, and argues conceptually and set the stage for their future use to effectively and meaningfully examine the relationships between residential segregation and health.


A Review of the Applications and Biodegradation of Polyhydroxyalkanoates and Poly(lactic acid) and Its Composites.
Overconsumption of plastic goods and improper handling of petroleum-derived plastic waste have brought a plethora of negative impacts to the environment, ecosystem and human health due to its recalcitrance to degradation. These drawbacks become the main driving force behind finding biopolymers with the degradable properties. With the advancement in biopolymer research, polyhydroxyalkanoate (PHA) and poly(lacyic acid) (PLA) and its composites have been alluded to as a potential alternative to replace the petrochemical counterpart. This review highlights the current synthesis process and application of PHAs and PLA and its composites for food packaging materials and coatings. These biopolymers can be further ameliorated to enhance their applicability and are discussed by including the current commercially available packaging products. Factors influencing biodegradation are outlined in the latter part of this review. The main aim of this review article is to organize the scattered available information on various aspects of PHAs and PLA, and its composites for packaging application purposes. It is evident from a literature survey of about 140 recently published papers from the past 15 years that PLA and PHA show excellent physical properties as potential food packaging materials.


Weaning patients from mechanical ventilation. How to avoid difficulty.
The majority of patients can be easily weaned from mechanical ventilation, but a substantial minority pose considerable difficulty. In such cases, the cause of ventilator dependency should be identified and correctable factors should be rectified. An organized plan of management, a team approach, optimal pulmonary and general patient care, and nutritional supplementation are important factors in successful weaning.


Scanning electron microscopic studies on the embryonic development of the surface structures of the paraventricular organ in the Brown Leghorn chicken.
The development of the surface specialization of the paraventricular organ (PVO) was studied in the domestic chicken from the 10th embryonic day to the day of hatching by scanning electron microscopy. On the 10th embryonic day, the ventricular surface of the PVO was found to be covered with many oval-shaped processes. On the 12th embryonic day, an additional kind of elongated processes appeared in the dorsal area of the ventricular surface of the organ. From the 16th to 18th embryonic day, such elongated processes were present on the entire ventricular surface of the PVO. At the same stage, the elongated processes in the dorsal portion of the PVO began to form small, meshed networks over the surface of the ependyma. Both the oval-shaped processes and the elongated processes are thought to be dendritic terminals of the PVO neurons.


Colometer: a real-time quality feedback system for screening colonoscopy.
To investigate the performance of a new software-based colonoscopy quality assessment system. The software-based system employs a novel image processing algorithm which detects the levels of image clarity, withdrawal velocity, and level of the bowel preparation in a real-time fashion from live video signal. Threshold levels of image blurriness and the withdrawal velocity below which the visualization could be considered adequate have initially been determined arbitrarily by review of sample colonoscopy videos by two experienced endoscopists. Subsequently, an overall colonoscopy quality rating was computed based on the percentage of the withdrawal time with adequate visualization (scored 1-5; 1, when the percentage was 1%-20%; 2, when the percentage was 21%-40%, etc.). In order to test the proposed velocity and blurriness thresholds, screening colonoscopy withdrawal videos from a specialized ambulatory colon cancer screening center were collected, automatically processed and rated. Quality ratings on the withdrawal were compared to the insertion in the same patients. Then, 3 experienced endoscopists reviewed the collected videos in a blinded fashion and rated the overall quality of each withdrawal (scored 1-5; 1, poor; 3, average; 5, excellent) based on 3 major aspects: image quality, colon preparation, and withdrawal velocity. The automated quality ratings were compared to the averaged endoscopist quality ratings using Spearman correlation coefficient. Fourteen screening colonoscopies were assessed. Adenomatous polyps were detected in 4/14 (29%) of the collected colonoscopy video samples. As a proof of concept, the Colometer software rated colonoscope withdrawal as having better visualization than the insertion in the 10 videos which did not have any polyps (average percent time with adequate visualization: 79% ± 5% for withdrawal and 50% ± 14% for insertion, P < 0.01). Withdrawal times during which no polyps were removed ranged from 4-12 min. The median quality rating from the automated system and the reviewers was 3.45 [interquartile range (IQR), 3.1-3.68] and 3.00 (IQR, 2.33-3.67) respectively for all colonoscopy video samples. The automated rating revealed a strong correlation with the reviewer's rating (ρ coefficient= 0.65, P = 0.01). There was good correlation of the automated overall quality rating and the mean endoscopist withdrawal speed rating (Spearman r coefficient= 0.59, P = 0.03). There was no correlation of automated overall quality rating with mean endoscopists image quality rating (Spearman r coefficient= 0.41, P = 0.15). The results from a novel automated real-time colonoscopy quality feedback system strongly agreed with the endoscopists' quality assessments. Further study is required to validate this approach.


Traumatic scapulothoracic dissociation: case report.
A 23-year-old man suffered traumatic scapulothoracic dissociation (TSD) in a car-vs.-bicyclist accident. TSD is a devastating forequarter injury characterized by brachial plexus damage, major upper extremity musculoskeletal disruption, and exsanguinating hemorrhage: our patient survived a hematocrit of 7. Prompt recognition and aggressive management of TSD's multiple injuries are crucial.


[Transient global amnesia following the use of ergots in the treatment of migraine].
Transient global amnesia (TGA) is defined as a selective, or almost selective, deficit of the memory that appears suddenly and lasts less than 24 hours. The aetiopathogenesis of this syndrome remains unknown and different theories have been put forward about its epileptic or ischemic origin, or the relationship that exists with the neuronal depression that is produced in migraine. A number of triggering factors have been described, including the taking of distinct pharmaceutical preparations. We report the cases of two patients with a history of migraines who suffered TGA after taking ergotamine and dihydroergotamine, respectively, to treat an attack of migraine. Given the vasoconstriction effect of these drugs, it was concluded that in both cases the main factor that triggered the TGA was the ingestion of ergots.


A common presentation of uncommon disease - Biliary Fasciola Hepatica.
Hepatobiliary fascioliasis is one of the rare but important parasitic infection in endemic areas such as Pakistan. Clinical manifestations overlap with common clinical conditions such as hepatitis and biliary stones causing common bile duct obstruction. Fascioliasis is a zoonotic infection caused by a leaf-shaped organism known as Fasciola Hepatica. Humans are accidentally infected by consuming contaminated water or food, especially undercooked cattle and sheep liver or raw green vegetables. We report three cases with similar clinical manifestations presenting in two different cities in Pakistan. After detailed clinical evaluation and laboratory investigations, the diagnosis was established by abdominal ultrasound and diagnostic and therapeutic cholangiography. Patients were followed till complete resolution of their symptoms and normalisation of liver function tests.


[Expression of apoptosis of the skin lesion and muscle from patients with dermatomyositis].
This study inquired into the relationship between the influence of corticosteroid and the expression of apoptosis, Fas and Bcl-2 in muscle from patients with dermatomyositis (DM). Corticosteroid was given to group A (10 DM cases) but not given to group B (12 DM cases). Apoptotic cells were detected in situ by terminal deoxynucleotidyl transferase-mediated-dUTP nick end labeling (TUNEL). Fas and Bcl-2 expressions was determined with the use of immunohistochemical staining in DM. The results showed that more expression of apoptosis in keratinocytes, muscle cells and lymphocytes were observed in group A. The apoptotic index (AI) of muscle cells and that of lymphocytes were more marked in group A than in group B (P < 0.05). Less apoptosis cells were observed in two weeks of treatment, and no correlation was found between apoptosis and the lesion of skin and muscle. The authors suggest that corticosteroid may play a role in inducing the apoptosis of keratinocytes, muscle cells and lymphocytes, which may be one of the therapeutic mechanisms of corticosteroid. The length of administering corticosteroid to the patients seems related to apoptosis.


The Correlation of Diabetes Mellitus and Urinary Retention From Intravesical OnabotulinumtoxinA Injection for Overactive Bladder.
The objective was to determine whether patients with diabetes mellitus (DM) treated with intravesical onabotulinumtoxinA (BoNT) injection for overactive bladder (OAB) had increased urinary retention requiring clean intermittent catheterization (CIC), as well as the impact of disease duration and severity. We hypothesize that patients with DM will have higher rates of retention after BoNT injection. We performed a retrospective cohort analysis of women in the Kaiser Permanente Southern California Health System who underwent BoNT injection for OAB, excluding women with a history of urinary retention or neurogenic bladder. We identified 565 patients, 410 in the control group and 155 in the DM group. No significant difference was found in the rate of CIC (9% in the control group versus 5.8% in the DM group, P = 0.2), voiding dysfunction, and peak postprocedure postvoid residual volume (PVR). Patients with diabetes had a significantly increased rate of postprocedure urinary tract infection (UTI; 27.6% versus 38.1%, P = 0.02). Urinary tract infection was significantly associated with urinary retention (adjusted odds ratio [OR], 2.26; 95% confidence interval [CI], 1.02-4.99; P = 0.045) and peak PVR ≥200 mL (adjusted OR, 2.42; 95% CI, 1.15-5.06; P = 0.019). Diabetic disease duration and severity were not a predictor of urinary retention, elevated PVR, or voiding dysfunction; however, the presence of ≥1 disease-related complication was a predictor of UTI (adjusted OR, 2.81; 95% CI, 1.34-5.91; P = 0.006). Diabetic patients had a similar rate of urinary retention requiring CIC after BoNT injection for OAB compared with nondiabetic patients. Diabetic patients had an increased risk of UTI based on disease severity.


Lentinula edodes produces a multicomponent protein complex containing manganese (II)-dependent peroxidase, laccase and beta-glucosidase.
A multicomponent protein complex containing manganese (II)-dependent peroxidase, laccase and beta-glucosidase was isolated from culture extracts of the white rot basidiomycete Lentinula edodes. This protein complex showed a single protein band on native polyacrylamide gel electrophoresis (PAGE). On sodium dodecyl sulfate (SDS)-PAGE, however, it displayed three major bands and several additional minor bands ranging in size from 60 kDa to 180 kDa, suggesting it being a complex of six to eight different proteins. The molecular mass of this complex was estimated to be approximately 660 kDa from the elution position of gel filtration. This enzyme complex was effective in transforming environmentally persistent xenobiotics, pentachlorophenol and 2,5-dichlorophenol.


An empirical assessment of the tripartite nexus between environmental pollution, economic growth, and agricultural production in Sub-Saharan African countries.
A lot of attention has been paid to environmental pollution worldwide, due to the increase in anthropogenic activities. Massive investment in non-renewable energy options raises questions regarding environmental sustainability and how to maximize food and non-food output while still preserving a healthy ecosystem. To this end, the present study explores the three-way nexus between economic growth, CO2 emission, and agriculture-value added will accounting for other control variables across a balanced panel of selected African economies from 1997 to 2020. Panel econometrics method of the generalized method of moments (two-step difference GMM) is used to obtain a robust result. From the present study, the environmental pollution model shows that economic growth significantly contributes to environmental pollution in Africa. Additionally, the food price index, capital, and FDI promote pollution, while agricultural production and labor decrease pollution. In the case of the economic growth model, the findings reveal that environmental pollution supports the growth-led pollution hypothesis. Also, the food price index and capital ameliorate economic growth, while foreign direct investments decrease economic growth. Finally, the agricultural production model indicates that economic growth increases agricultural production when the interaction term between GDPC and FDI is included in the model. In summary, the combination of explanatory variables, environmental pollution, capital, and foreign direct investment decreases agricultural production. On the contrary, the food price index and labor promote agricultural production in Africa. Furthermore, the study provides a lot of policies for authorities and stakeholders in Sub-Saharan African countries and other developing economies.


Long-term follow-up of DYT1 dystonia patients treated by deep brain stimulation: an open-label study.
Long-term efficacy of internal globus pallidus (GPi) deep-brain stimulation (DBS) in DYT1 dystonia and disease progression under DBS was studied. Twenty-six patients of this open-label study were divided into two groups: (A) with single bilateral GPi lead, (B) with a second bilateral GPi lead implanted owning to subsequent worsening of symptomatology. Dystonia was assessed with the Burke Scale. Appearance of new symptoms and distribution according to body region were recorded. In the whole cohort, significant decreases in motor and disability subscores (P < 0.0001) were observed at 1 year and maintained up to 10 years. Group B showed worsening of the symptoms. At 1 year, there were no significant differences between Groups A (without subsequent worsening) and B; at 5 years, a significant difference was found for motor and disability scores. Within Group B, four patients exhibited additional improvement after the second DBS surgery. In the 26 patients, significant difference (P = 0.001) was found between the number of body regions affected by dystonia preoperatively and over the whole follow-up. DBS efficacy in DYT1 dystonia can be maintained up to 10 years (two patients). New symptoms appear with long-term follow-up and may improve with additional leads in a subgroup of patients.


The wolf is crying in the operating room: patient monitor and anesthesia workstation alarming patterns during cardiac surgery.
Vital sign monitors and ventilator/anesthesia workstations are equipped with multiple alarms to improve patient safety. A high number of false alarms can lead to a "crying wolf" phenomenon with consecutively ignored critical situations. Systematic data on alarm patterns and density in the perioperative phase are missing. Our objective of this study was to characterize the patterns of alarming of a commercially available patient monitor and a ventilator/anesthesia workstation during elective cardiac surgery. We performed a prospective, observational study in 25 consecutive elective cardiac surgery patients. In all patients, identically fixed alarm settings were used. All incoming patient data and all alarms from the patient monitor and the anesthetic workstation were digitally recorded. Additionally, the anesthesia workplace was videotaped from 2 different angles to allow retrospective annotation and correlation of alarms with the clinical situation and assessment of the anesthesiologists' reaction to the alarms. Of the 8975 alarms, 7556 were hemodynamic alarms and 1419 were ventilatory alarms. For each procedure, 359 ± 158 alarms were recorded, representing a mean density of alarms of 1.2/minute. Approximately 80% of the total 8975 alarms had no therapeutic consequences. Implementation of procedure-specific settings and optimization in artifact and technical alarm detection could improve patient surveillance and safety.


Long-range interfacial electron transfer of metalloproteins based on molecular wiring assemblies.
We address some physical features associated with long-range interfacial electron transfer (ET) of metalloproteins in both electrochemical and electrochemical scanning tunneling microscopy (ECSTM) configurations, which offer a brief foundation for understanding of the ET mechanisms. These features are illustrated experimentally by new developments of two systems with the blue copper protein azurin and enzyme nitrite reductase as model metalloproteins. Azurin and nitrite reductase were assembled on Au(111) surfaces by molecular wiring to establish effective electronic coupling between the redox centers in the proteins and the electrode surface for ET and biological electrocatalysis. With such assemblies, interfacial ET proceeds through chemically defined and well oriented sites and parallels biological ET. In the case of azurin, the ET properties can be characterized comprehensively and even down to the single-molecule level with direct observation of redox-gated electron tunnelling resonance. Molecular wiring using a pi-conjugated thiol is suitable for assembling monolayers of the enzyme with catalytic activity well-retained. The catalytic mechanism involves multiple-ET steps including both intramolecular and interfacial processes. Interestingly, ET appears to exhibit a substrate-gated pattern observed preliminarily in both voltammetry and ECSTM.


Stroke volume variation as an index of fluid responsiveness can be impaired by mental stress.
Cardiac stroke volume variation (SVV) measurement is one of the techniques to detect fluid-responsive hypovolemia in patients under mechanical ventilation. There is an ongoing effort to apply SVV for this purpose also in conscious patients. However, the effect of mental stress often occurring in conscious patients as a potential confounding factor on SVV is not known. The aim of our study was to compare effect of simulated hypovolemia and mental stress on SVV in healthy volunteers in the context of potential confounders - breathing pattern, respiratory sinus arrhythmia magnitude and sex. We examined 102 young healthy volunteers (58 females), mean age 18.6 years. Finger arterial blood pressure was recorded by volume-clamp photoplethysmographic method (Finometer Pro, FMS, Amsterdam, Netherland). From the blood pressure curve, a built in ModelFlow algorithm calculated stroke volume values (SV) for each heartbeat. Respiratory volume was recorded using calibrated respiratory inductive plethysmography (RespiTrace, NIMS, Miami Beach, FL, USA). During four phases of examination protocol (supine rest, head-up tilt (HUT), supine recovery, mental arithmetic task (MA)) we analyzed SVV related to respiratory activity. While during HUT we found an expected increase in SVV together with mean SV decrease, SVV significantly decreased during MA. The observed changes during MA could be attributed to an increased respiratory rate and/or decreased respiratory sinus arrhythmia. Sex related differences in SVV responses to HUT and MA were observed. We conclude that mental stress together with respiratory sinus arrhythmia and respiratory pattern changes can significantly influence SVV as a potential index of fluid responsiveness in conscious patients.


Improving the efficiency of Rubisco by resurrecting its ancestors in the family Solanaceae.
Plants and photosynthetic organisms have a remarkably inefficient enzyme named Rubisco that fixes atmospheric CO2 into organic compounds. Understanding how Rubisco has evolved in response to past climate change is important for attempts to adjust plants to future conditions. In this study, we developed a computational workflow to assemble de novo both large and small subunits of Rubisco enzymes from transcriptomics data. Next, we predicted sequences for ancestral Rubiscos of the (nightshade) family Solanaceae and characterized their kinetics after coexpressing them in Escherichia coli. Predicted ancestors of C3 Rubiscos were identified that have superior kinetics and excellent potential to help plants adapt to anthropogenic climate change. Our findings also advance understanding of the evolution of Rubisco's catalytic traits.


Recruitment of DNA damage checkpoint proteins to damage in transcribed and nontranscribed sequences.
We developed a chromatin immunoprecipitation method for analyzing the binding of repair and checkpoint proteins to DNA base lesions in any region of the human genome. Using this method, we investigated the recruitment of DNA damage checkpoint proteins RPA, Rad9, and ATR to base damage induced by UV and acetoxyacetylaminofluorene in transcribed and nontranscribed regions in wild-type and excision repair-deficient human cells in G1 and S phases of the cell cycle. We find that all 3 damage sensors tested assemble at the site or in the vicinity of damage in the absence of DNA replication or repair and that transcription enhances recruitment of checkpoint proteins to the damage site. Furthermore, we find that UV irradiation of human cells defective in excision repair leads to phosphorylation of Chk1 kinase in both G1 and S phase of the cell cycle, suggesting that primary DNA lesions as well as stalled transcription complexes may act as signals to initiate the DNA damage checkpoint response.


Glycoqueuing: Isomer-Specific Quantification for Sialylation-Focused Glycomics.
Changes of α-2,3-/α-2,6-linked sialic acids (SAs) in sialylglycans have been found to be closely related with some diseases. However, accurate quantification of sialylglycans at the isomeric level remains challenging due to their instability, structural complexity, and low mass spectrometry (MS) detection sensitivity. Herein, we propose an analytical strategy named "glycoqueuing", which allows sequential chromatographic elution and high-sensitivity MS quantification of various sialylglycan isomers based on isotopic labeling followed by analysis via online reversed-phase high performance liquid chromatography coupling with MS (RP-HPLC-MS). The new method was validated by detailed structural identification and quantification of fetal bovine serum (FBS) N-linked sialylglycan isomers, during which many branching isomers were successfully differentiated, and 28 sialylglycan compositions with Neu5Gc residues were analyzed. The method was successfully applied to isomer-specific, quantitative comparison of sialylated N-glycans between bovine and rabbit immunoglobulin G (IgG) and the search for serum sialylated N-glycan biomarker candidates of hepatocellular carcinoma, during which a 55% increase of α-2,6-sialylated fucosylated N-glycans was revealed, demonstrating the great applicability and potential clinical usage of the method.


Essential oil for the control of fungi, bacteria, yeasts and viruses in food: an overview.
This review begins with a general introduction to essential oils (EO) and their relation to food and microorganisms. Classification and characteristics of EO, addressing the major compounds with antimicrobial action. Subsequently, the main microorganisms followed by a collection of the main works published in recent years that approached the influence of the EO on the protection against microorganisms and food decontamination. At last, the major gaps and future perspectives on the subject. Using EO for fighting food contamination is a way of sustainably supplying the need for new antimicrobials to ensure microbial safety and is a viable source to solve the problem of current microbial resistance. Form of application, EO composition and microbiological load are reported as the responsible factors for the treatment's success. The EO's effects on fungi and bacteria are already well known, but its effect on viruses and yeasts is something to be explored.


Ruptured aneurysm of the sinus of Valsalva in association with persistent left superior vena cava--a case report.
A 58-year-old man presenting with chest pain and dyspnea was diagnosed by transesophageal echocardiography and cardiac catheterization to have the rare combination of ruptured aneurysm of noncoronary sinus of Valsalva into the right ventricle in association with persistent left superior vena cava. These defects were confirmed at cardiac surgery. This case shows the importance of complementary use of invasive and noninvasive methods together in the diagnosis of rare combinations of lesions.


[Swiss pacemaker statistics in 1983].
The data on 98% of pacemakers implanted in 1983 in Switzerland were analyzed and compared with previous years. The number of first implantations slightly increased to 240 per million population per year (1982: 216). 80% of pacemakers used were multiprogrammable, and 7.7% were physiological pacemakers. Counting only the centers implanting physiological pacemakers, the number is 14.5%. Complications demanding reinterventions decreased slightly. This applied especially to complications related to implantation techniques.


[Relationship between auditory disability and auditory threshold in acute acoustic trauma: pilot study].
The aim of this study was to determine the relationship existing between auditory disability, according to WHO 1980, and pure tone audiometry threshold in noise induced hearing loss. Disability was evaluated on the basis of a questionnaire submitted to 286 subjects with acoustic trauma. Answers obtained were considered reliable on the basis of statistical analysis. Results showed that subjects with disability have an higher pure tone threshold than subjects without auditory disability. However it appears difficult to determine a precise threshold level ever which auditory disability may be considered present. The Authors suggest that this limit could be determined on the basis of pure tone threshold at the 10th centile of the group of subjects with disability or at the 90th centile of subjects without disability.


Lectin activity as a marker for Hodgkin disease cells.
Treatment of cultured Hodgkin disease (HD) cells with neuraminidase results in decreased reactivity of monoclonal antibody VIM-D5 with its antigen, the X hapten, a fucosyl-N-acetyllactosamine. The other feature characteristic of HD cells is the expression of high levels of ectosialyltransferase activity. We present evidence for a cause-effect relationship between these two findings in that VIM-D5 antigenicity can be restored on neuraminidase-treated HD cells by modulating transferase activity. This can be interpreted in terms of a lectin activity of the ectosialyltransferase that binds the X hapten's desialylated galactosyl residues, thereby preventing antigen recognition by VIM-D5 antibody. This proposed mechanism is indistinguishable from the autoinhibition phenomenon described for another galactophilic binding protein, the hepatic binding protein (HBP), which binds its own terminal galactosyl residues following neuraminidase treatment. We establish a close relationship between the HD galactophilic binding site and HBP in that antiserum to HBP (i) inhibits the neuraminidase-induced loss of VIM-D5 antigenicity, (ii) blocks the binding of asialoglycoprotein to hepatocytes after being absorbed by and eluted from HD cells, and (iii) recognizes a single HD protein, which in its high level of expression is unique to HD cells. The presence of lectin activity in its classic sense on the surface of HD cells is confirmed by the erythrocyte-agglutinating ability of these cells. This lectin activity, which appears to be related to an ectosialyltransferase on the surface of HD cells, may serve as a marker for the abnormal cells characteristic of HD.


Influence of "Hospital-Community-Family" Integrated Management on Blood Pressure, Quality of Life, Anxiety and Depression in Hypertensive Patients.
To explore the Influence of "hospital-community-family" integrated management on blood pressure, quality of life, anxiety and depression in hypertensive patients. A total of 60 patients with hypertension were treated in our hospital from July 2019 to July 2021. The patients were randomly divided into control group (n =30) and study group (n =30). The former accepts routine management, while the latter accepts "hospital-community-family" integrated management. Nursing satisfaction, blood pressure, disease awareness rate, anxiety and depression scores, disease control ability and quality of life scores were compared. First of all, we compared the nursing satisfaction: the study group was very satisfied in 25 cases, satisfactory in 4 cases, general in 1 case, the satisfaction rate was 100.00%, while in the control group, 10 cases were very satisfied, 8 cases were satisfied, 7 cases were general, and 5 cases were dissatisfied, the satisfaction rate was 83.33%; The nursing satisfaction of the study group was higher than that of the control group (P <0.05). Secondly, we compared the level of blood pressure. There was no significant difference before management (P >0.05) but the blood pressure decreased after treatment. In the control group, the level of blood pressure in the study group was lower than that in the control group (P <0.05). In terms of disease awareness rate the scores of hypertension related knowledge hypertension harmfulness community management methods regular reexamination and blood pressure monitoring in the study group were significantly higher than those in the control group (P <0.05). There was no significant difference in anxiety and depression scores before treatment (P >0.05), but decreased after treatment. Compared with the control group, the anxiety and depression scores of the study group were lower (P <0.05). In terms of disease control ability, the total scores of diet management, medication management, behavior management and information management in the study group were higher compared to the control group (P <0.05). Finally, we compared the scores of qualities of life. Before management, there exhibited no significant difference (P >0.05). After management, the scores of quality of life decreased. Compared to the control group, the scores of physiological function, psychological function, social function and health self-cognition in the study group were lower than those in control group (P <0.05). The application of integrated "hospital, community and family" management can vertically integrate medical resources and establish a truly effective hierarchical treatment model. Integrated "hospital-community-family" management can improve patient compliance with treatment, enhance patients' self-management ability and confidence, and improve the management efficiency of medical staff.


Posting and Transfer: the experiences of public sector doctors in two Indian states.
Posting and Transfer (PT) refers to deployment of the health workforce in ways that ensure appropriate numbers and distribution. Although PT is a crucial aspect of health workforce governance, it remains under-researched from the viewpoint of implementation, health workforce and governance. The aim of this paper is to examine public sector doctors' experience of their initial postings, in the context of local policy from two Indian states. We carried out a review search for policy documentation. A total 61 in-depth interviews were conducted in both states with 33 doctors, as subjects of the study. There were 28 key informant (KI) interviews of health administrators and other policy actors to understand their perspectives of PT policies and implementation. Thematic analysis was used to analyse data. Job histories were constructed from the doctors' interviews to track their experience with the PT system, and analysed using location, duration and postings. Despite search for state policy for PT, we were unable to identify any policy documentation. However, participants referred to PT practices that suggested expectations of what the poliy meant to them. These expectations were corroborated by KI, and the job histories and interview data enabled the authors to construct a series of norms, interpreted as evidence of implied policy. The main norms identified relate to service need, native place, request, gender and posting duration. The norm related to state need had strong face validity, while other norms based on request, gender and duration were less consistent in application. In the absence of documented policies, the construction of norms from the qualitative data proved useful to examine the dynamics of health workers' interactions with the initial PT systems This construction of norms provides a methodological innovation allowing health policy and systems researchers to compensate for the absence of documented policy in exploring PT functions.


The complete mitochondrial genome of Sargassum kjellmanianum (Sargassaceae) and phylogenetic analysis of Sargassum kjellmanianum (Sargassaceae).
Sargassum kjellmanianum plays an important role in marine ecosystem and biological resource utilization. Here, we analyzed the characteristics and evolution of mitochondrial genome of S. kjellmanianum by paired-end sequencing. The complete mitogenome comprises a circular DNA molecule measuring 34,723 bp in length with 35 coding genes. The circular genome consisted of seven protein-coding genes, 25 tRNA genes, and three rRNA genes, with a total length of 26,553 bp. The overall A + T content was 63.43%, higher than the G + C content (36.57%). Phylogenetic analysis confirmed S. kjellmanianum was closely clustered with S. muticum.


A case report of systemic capillary leak syndrome (Clarkson's disease).
Systemic capillary leak syndrome (SCLS) is a very rare disorder also known as Clarkson's disease. The condition is characterized by recurrent episodes of severe capillary hyperpermeability resulting in severe hemoconcentration, hypoalbuminemia, hypovolemia and shock. We describe a 41-year-old previously healthy man who was admitted to hospital on several occasions with rapidly developing hypovolemic shock accompanied by extreme hemoconcentration and hypoalbuminemia. Our case is similar to other reports describing patients with SCLS where the initial suspicions have been pointing towards septic shock. He received a combination of prophylactic treatment with theophylline, beta-agonists, immunoglobulins and statins but eventually died after a severe episode of SCLS that ended with recurrent cardiac arrest. Clinical autopsy revealed pulmonary edema and acute and chronical organic fluid overload. SCLS should be kept in mind when treating patients suffering from attacks of severe idiopathic edema and mimics recurrent septic shock where no pathogen is found. The pathogenesis is unknown and the attacks may be lethal.


Glycoprotein gD of MDV lacks functions typical for alpha-herpesvirus gD homologues.
Glycoprotein D (gD) belongs to family of conserved structural proteins of alpha-herpesviruses. During productive infection of cells by herpes simplex virus 1 (HSV-1) gD has several important functions, is involved in virus penetration to and release from infected cells and is one of main targets of neutralizing antibodies. Similar functions are shared also by other alpha-herpesvirus gD homologues. Surprisingly, in previous studies it was found that MDV gD expression could not be detected during infection in vitro using immunological methods. In this study we have analyzed expression of MDV gD and its biological consequences. In vitro expression using rabbit reticulocyte lysate and/or overexpression in transfected cells showed that the second ATG codon is required for synthesis of mature, glycosylated gD. In addition, it was found that gD overexpression is neither toxic for transfected cells nor is involved in membrane fusion. After MDV infection of a proprietary cell line stably transfected with plasmid overexpressing MDV gD, no viral particles could be found in culture. On the other hand, cells overexpressing the MDV gD were sensitive to MDV infection in similar way as parental, non-transfected cells. From our study and results of other authors we propound the following conclusions: (i) MDV gD expression is blocked during in vitro infection at transcription level; (ii) MDV gD is lacking many important functions characteristic for other alpha-herpesvirus gD homologues; (iii) overexpression of single MDV gD does not result in production of mature infectious MDV particles.


Amnion membrane proteins attenuate LPS-induced inflammation and apoptosis by inhibiting TLR4/NF-κB pathway and repressing MicroRNA-155 in rat H9c2 cells.
Amnion membrane (AM) has been popular for the treatment of inflammatory disorders due to its cell repairing properties. This current study aims to find the underlying mechanisms of amnion membrane proteins (AMPs) against the pro-inflammatory miRNA, miR-155, miR-146, and anti-apoptotic microRNA, miR-21, in LPS-treated H9c2 cells. Cell viability and apoptosis were determined by MTT assay and annexin V/PI staining. The production of the cytokines, TNF-α and IL-6 were evaluated by using qPCR and Enzyme-linked immunosorbent assay (ELISA), respectively. In addition, the expression of miRNAs was quantified by qPCR, and also the protein level of TLR4 and NF-kβ was determined with western blotting. We found that AMPs ameliorated LPS-induced reduction of cell viability and augment apoptosis in H9c2 cells. AMPs efficiently inhibited cytokine expression (IL-6 and TNF-α) and activity of TLR4/NF-κB pathway in LPS-treated H9c2 cells. Correspondingly, in parallel with the suppression of pro-inflammatory cytokines and apoptosis, AMPs mitigated pro-inflammatory miRNA, miR-155 expression, while, the expression of miR-155 was found to be increased in LPS-treated H9c2 cells. Also, AMPs activated miR-146 expression in H9c2 cells under LPS treatment. Additionally, the elevated expression of miR-21 provoked by LPS was further enhanced by AMPs. In conclusion, AMPs could alleviate LPS-induced cardiomyocytes cells injury via up-regulation of miR-21, miR-146, and suppression of TLR4/NF-κB pathway, which plays a key role in the down-regulation of LPS-mediated miR-155 and inflammatory cytokine expression.


CTL and serologically defined antigens of B2m,H-3 region.
The antigens of the B2m,H-3 region of 13 chromosome 2 congenic strains and seven inbred strains have been studied by using CML and serologic techniques. Nine patterns of cross-reactivity have been defined by CML assays. These results are in agreement with an extend previously described cross-reactivity studies. The reactivities of three monoclonal antibodies previously thought to be reacting with B2M-B are shown to differ: Ly-m11 and J-5 react with cells of strain B10-pa,at and clone 23 does not. Two H-3 region loci are hypothesized on the basis of CML and serologic activity: B2m and H-3. The CTL responses to the B2M antigens are H-2K restricted; the CTL responses to H-3 antigens are H-2D restricted. The restriction of the response to the H-3 antigen requires effector-target identity of the H-2D molecule but not the B2M molecule of the class I antigen. These loci have been separated by recombination from H-42 in the production of the congenic strain B10.FS-a. A gene order of B2m, H-3, H-42 is suggested.


[Hyperthermia: microwave hyperthermia in combination with intra-arterial infusion chemotherapy of cancer of the pancreas].
Fourty eight patients with cancer of head of pancreas have been treated by the intra-arterial infusion of 5-FU and Mitomycin C alone or in combination with regional hyperthermia, employing microwave machine operating at a frequency of 2450 MHz. In patients treated with intra-arterial infusion chemotherapy alone the average survival of 4.2 month was attained, whereas the average survival of 9.0 month has been seen in 39 patients treated with infusion chemotherapy and hyperthermia. The hyperthermia treatment has improved the local therapeutic effects and the effects on the survival of the patients. Thanks to this combination therapy 27 of 39 patients (69%) survived more than 6 month, and 12 patients (31%) survived more than one year, longest survival being 7 years. This study confirms that heat administered by the microwave unit potentiated the effects of the intraarterial infusion chemotherapy.


Combined treatment with acetazolamide and cisplatin enhances chemosensitivity in laryngeal carcinoma Hep-2 cells.
The aim of the present study was to determine whether acetazolamide (Ace) treatment enhances the chemosensitivity of Hep-2 laryngeal cells to cisplatin (Cis). At the logarithmic growth phase, Hep-2 cells were treated with Ace, Cis or both, and cell viability was detected using an MTT assay. The degree of apoptosis was detected using flow cytometry. Expression levels of apoptosis-related proteins, including BCL2 apoptosis regulator (bcl-2), BCL2 associated X (bax) and caspase-3, and of proliferation-related proteins, including proliferating cell nuclear antigen (PCNA) and tumor protein p53 (P53), were detected using western blotting. mRNA expression levels of aquaporin-1 (AQP1) in each group were detected using reverse transcription-polymerase chain reaction. Compared with the drugs used alone, treatment with both Ace and Cis displayed synergistic effects on the growth inhibition and apoptosis induction in Hep-2 cells. The Ace/Cis combination decreased the expression of PCNA but increased the expression of p53. In addition, the combination treatment decreased the ratio of bcl-2/bax and increased the expression of caspase-3, as well as decreased the expression of AQP1. These results demonstrated that the combined use of Ace and Cis enhanced the chemosensitivity of laryngeal carcinoma cells.


Two-dimensional MoSe2 nanosheets via liquid-phase exfoliation for high-performance room temperature NO2 gas sensors.
Molybdenum selenide (MoSe2) has drawn significant interest due to its typical semiconductor properties. MoSe2 is a relatively novel material in the field of gas sensors especially at room temperature. Herein, we utilize a facile and efficient synthetic method of liquid-phase exfoliation to exfoliate bulk MoSe2 into nanosheets. Anhydrous ethanol is used as dispersant, so the low boiling point makes it easy to be removed from MoSe2 nanosheets, which does not affect the subsequent sensing performance. The exfoliated few-layered MoSe2 nanosheets shows significantly enhanced NO2 gas response (1500% to 10 ppm NO2 which is 18 times greater than pristine bulk MoSe2), a low detection concentration (50 ppb), an outstanding repeatability, a remarkable selectivity, and a reliable long-term device durability (more than 60 d) at room temperature (25 °C). The reason of the significant improvement in gas sensing performance can be attributed mainly to the higher surface-to-volume ratio of exfoliated MoSe2 nanosheets. It promotes the adsorption of gas molecules on the surface of the material, thereby facilitating the charge transfer process. The superior performance of this gas sensor makes MoSe2 nanosheets a potential candidate for room temperature NO2 detection.


Computer visualization techniques (CVTs) foster evidence-based target delineation.
Computer visualization techniques (CVTs) are an emerging technology that can organize all cancer specialists. This article describes CVTs' ability to maximize the currently untapped advantages of intensity modulated radiotherapy (IMRT). The visual speed and dynamic strategies inherent in CVTs improves IMRT by distilling vast amounts of anatomic, multimodal imaging, textual/meaning, and surgical/outcome data into a large, rigorous, standardized evidence base of storable target delineation plans. This ability to standardize strategies will allow the collection of meaningful evidence based outcome data.


[Breast cancer surgery in Norway 1990-95 illustrated by data from SINTEF United].
Breast-conserving therapy has been shown to be as effective as mastectomy in many cases; hence in many countries more breast cancer patients are offered this type of treatment. This study focuses on the amount and type of surgery used in Norway for breast cancer patients and the possible use of hospital discharge data to evaluate the diffusion of this surgical practice. Data from the nationwide Register of Hospital Discharges in Norway at SINTEF Unimed for patients operated for breast cancer from 1990 to 1995 were used. 11,041 patients were registered with 11,727 hospital admissions for breast cancer operations from a total of 64 hospitals. The discrepancy in the number of breast cancer patients with the National Cancer Registry was 7%. Breast-conserving surgery was performed in 19.7%. An increase from 17% in 1990 to 21% in 1995 was found, but with variations according to type of hospital, county and age of patients. The percentage of breast conserving surgery is still low in Norway; this indicates that many women are not offered this type of surgery. With some caution, the data from SINTEF Unimed can be used to reflect the clinical practice over time at Norwegian hospitals. Further improvements could be obtained if national identity numbers were added to the database.