Delayed cardioprotective effects of WY-14643 are associated with inhibition of MMP-2 and modulation of Bcl-2 family proteins through PPAR-α activation in rat hearts subjected to global ischaemia-reperfusion.
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors regulating cardiac lipid metabolism and energy homeostasis. Although the activation of PPARs has been implicated in cardioprotection, the molecular mechanisms are largely unexplored. In this study, we aimed to investigate the effect of the PPAR-α agonist WY-14643 (WY), mimicking a delayed effect of preconditioning in rat hearts exposed to acute ischaemia-reperfusion (I/R) 24 h later, and to define whether antioxidative and antiapoptotic mechanisms are involved. Treatment with WY markedly attenuated post-ischaemic contractile dysfunction (as evidenced by the reduced infarct size), the higher left ventricular developed pressure (LVDP) recovery, and the decreased occurrence of arrhythmias. These effects were abolished in the presence of the PPAR-α antagonist MK886. Heme oxygenase-1, a key antioxidative enzyme implicated in cytoprotection, was upregulated in response to WY at baseline, but was markedly reduced after I/R, indicating reduced oxidative stress. WY treatment was also associated with decreased mRNA levels and enzymatic activity of matrix metalloproteinase-2, and increased ratios of Bcl-2:Bax proteins. These results indicate that PPAR-α activation by its selective ligand WY may confer delayed preconditioning-like protection in rat hearts subjected to I/R by modulating oxidative stress, activation of matrix metalloproteinase-2, and expression of Bcl-2 and Bax.


The hamstring syndrome--a new gluteal sciatica.
The condition in which pain is felt over the area at the ischial tuberosity and radiating down the back of the thigh is labelled the hamstring syndrome. The pain is typically incurred by assuming a sitting position, stretching the affected leg or/and running fast. The symptoms are caused by tight, tendinous structures of the hamstring muscle at the area of its insertion into the ischial tuberosity. Following division of these structures, complete relief is obtained.


DNA mismatch repair in eukaryotes and bacteria.
DNA mismatch repair (MMR) corrects mismatched base pairs mainly caused by DNA replication errors. The fundamental mechanisms and proteins involved in the early reactions of MMR are highly conserved in almost all organisms ranging from bacteria to human. The significance of this repair system is also indicated by the fact that defects in MMR cause human hereditary nonpolyposis colon cancers as well as sporadic tumors. To date, 2 types of MMRs are known: the human type and Escherichia coli type. The basic features of the former system are expected to be universal among the vast majority of organisms including most bacteria. Here, I review the molecular mechanisms of eukaryotic and bacterial MMR, emphasizing on the similarities between them.


Immunolocalization of urokinase and its receptor in prematurely fused cranial sutures of infants.
In cranial sutural samples derived from five children with premature cranial suture fusion we have performed immunostaining for the urokinase plasminogen activator (uPA) and urokinase receptor (uPAR). We have found a strong reactivity for cell- or matrix-bound uPA and uPAR in the sutural connective tissue and associated with the osteoblasts and osteocytes lining the calvarial bone. The sutural tissue itself showed a banding with different intensity of urokinase and uPAR staining concerning connective tissue. It is proposed that the components of the plasminogen activating system are involved in tissue turnover of sutural tissue and in sutural growth.


Wine features related to safety and consumer health: an integrated perspective.
This review presents a global view of the current situation of the scientific knowledge about aspects of wine with possible repercussions (positive or negative) on consumer health and wine safety. The presence in wine of some potential harmful compounds such as phytosanitary products, trace metal compounds, sulfites, and some toxics of microbial origin, such as ochratoxin A, ethyl carbamate, and biogenic amines, is discussed. The different strategies and alternative methodologies that are being carried out to reduce or to avoid the presence of these substances in wines are also discussed. In recent years much work has focused on establishing the scientific explanations for the positive biological effects of some wine compounds. In this review, we also examine the latest knowledge regarding wine and health, focusing on two types of compounds that have been related to the positive effects of moderate wine consumption, such as phenolic compounds and bioactive peptides.


Associations between heat pain perception and pain severity among patients with chronic pain.
The primary aim of this study was to investigate the associations between standardized values of thermal sensory perception and standardized scores of clinical pain among a heterogeneous cohort of adults with chronic pain that included individuals receiving chronic opioid therapy. The study used a prospective design. The study was set in a multidisciplinary pain rehabilitation center at a tertiary medical center. The cohort included 163 patients (female 58%) who met inclusion criteria, and were admitted from March 2007 to June 2008. Using a validated quantitative sensory test method of levels, standardized values of heat pain (HP) perception and cooling detection threshold were obtained 1day following admission. Standardized scores of clinical pain were obtained at admission using the pain severity subscale of the Multidimensional Pain Inventory. At admission, 109 (67%) patients were using opioids, and the mean morphine equivalent dose was 192mg/day. The mean pain duration was 10.5years, and the two most frequent diagnoses were low back pain (29%) and headache (12%). A significant negative correlation was found between pain severity and HP threshold (r=-0.170, P=0.030), where lower values of HP threshold correlated with greater scores of pain severity. Post hoc linear regression analysis showed the association between HP threshold and pain severity retained statistical significance (P=0.039) after adjusting for opioid dose, pain duration and pain diagnosis. The use of standardized values of HP perception and clinical pain may be key methodological approaches for investigating the clinical correlates of HP perception among heterogeneous populations of adults with chronic pain.


Bacterial infections in burns patients: a three years study at RML Hospital, Delhi.
A study was undertaken at RML Hospital, Delhi to examine the bacterial infections of burn cases and determine the antibiograms of the isolates to commonly used antimicrobial agents. A total of 489 pus samples from as many patients received, over a period of three years (January 1992 to December, 1994) yielded 793 isolates. Pseudomonas sp. was the commonest (53.9%) followed by Klebsiella sp. (35.1%) Staphylococcus aureus (30.6%) Proteus sp. (23.5%). Esch. coli (14.1%) and others (4.9%). The most resistant isolate to commonly used antimicrobial was Klebsiella sp. (16.4%), followed by Esch. coli (15.4%) Pseudomonas sp. (15.2%) Proteus sp. (7.8%) and Staphylococcus aureus (4.6%). The infection of burn wounds with multiple organisms, with superadded problem of drug resistance, indicate the institution of a drug policy by the hospitals for burns patients.


Distribution of phthalate esters in agricultural soil with plastic film mulching in Shandong Peninsula, East China.
The content of phthalate esters (PAEs) was investigated in 36 vegetable fields with plastic film mulching in Shandong Peninsula, East China. Soils at depths of 0-10 cm, 10-20 cm, and 20-40 cm were collected, and 16 PAEs were analyzed by gas chromatography-mass spectrometry. PAEs were detected in all the analyzed samples. The total contents of the 16 PAEs (Σ16PAEs) ranged from 1.374 to 18.810 mg/kg, with an average of 6.470 mg/kg. Among the four areas of Shandong Peninsula, including Qingdao, Weihai, Weifang, and Yantai, the highest Σ16PAE in the soil was observed in Weifang district (9.786 mg/kg), which is famous for large-scale vegetable production. Despite the significant differences among the Σ16PAEs, the PAE compositions in soils with plastic film mulching in Shandong Peninsula were comparable. Diethyl phthalate (DEP), diisobutyl phthalate, and di(4-methyl-2-pentyl) phthalate were present in all the samples, whereas di-n-hexyl phthalate was detected only in Qingdao (∼1%) and dicyclohexyl phthalate was observed only in Weifang (5.7-8.2%) in low proportions. The ratios of dimethyl phthalate, DEP, and di-n-butyl phthalate, which exceeded allowable concentrations, were 63.9-100% at different soil depths, indicating high PAE pollution. The concentration of butyl benzyl phthalate detected only in Weifang exceeded the recommended allowable soil concentration. Overall, the high PAE content in the soil with plastic film mulching in Shandong Peninsula is an issue of concern because of the large amounts of plastic film used.


Dispersal of the Invasive Pasture Pest Heteronychus arator into Areas of Low Population Density: Effects of Sex and Season, and Implications for Pest Management.
African black beetle, Heteronychus arator (Scarabaeidae), is an exotic pest of pastures in northern New Zealand. Both adults and larvae feed on pasture grasses. Adults disperse by walking (short range) or flying (long range). Dispersal flights are triggered by warm night temperatures in spring and autumn. Short range adult dispersal in search of mates, food or oviposition sites is poorly understood. This study investigated walking activity of H. arator adults over three seasons in New Zealand pastures. Adult walking activity was monitored using pitfall traps along fence lines and in pasture plots on a dairy farm in Waikato, New Zealand, in spring 2013, spring 2014, and autumn 2015. Beetle populations were reduced by application of a biopesticide bait to compare walking activity between treated and control plots for up to 26 days post-treatment. Marked beetles were released into the pasture plots to measure the distance traveled by recaptured individuals. Trap catches along the fence lines were correlated with air temperatures in 2013. Trap catches were male biased in spring 2014 compared with autumn 2015. Trap numbers in the control plots were nearly double that of treated plots in both seasons. More beetles were caught in the pitfall traps at the edges of the treated plots than in the center. Trap catches were consistent throughout the control plot in spring 2014, but in autumn 2015 more beetles were caught in the center of the control plot than at the edges. Few marked beetles were recaptured with dispersal rates estimated as <0.5 m per day. Warmer temperatures encouraged short range dispersal in H. arator. Males were more active than females during the spring mating season. Edge effects were strong and should be considered in the design of field experiments.


Hereditary hemorrhagic telangiectasia: ENG and ALK-1 mutations in Dutch patients.
Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is an autosomal dominant disorder characterized by an aberrant vascular development. The resulting vascular lesions range from smaller mucocutaneous telangiectases to large visceral arteriovenous malformations, especially in the skin, lung, gastrointestinal tract and the brain. Mutations in the genes encoding endoglin (ENG, chromosome 9q34) and activin A receptor type-like kinase 1 (ALK-1, also named ACVRL1, chromosome 12q13) are associated with HHT1 and HHT2, respectively. We report here on the genetic and molecular heterogeneity found in the HHT population in the Netherlands. Probands of 104 apparently unrelated families were studied and we performed sequence analysis on both the ENG gene and ALK-1 gene. In most of the probands, we found a mutation in one of the two genes: 53% in the ENG gene and 40% in the ALK-1 gene. In 7% of the families no ENG or ALK1 mutation was found. The mutations detected were deletions, insertions, nonsense, missense and splice site mutations. The majority were novel mutations.


Update of New Daily Persistent Headache.
The diagnostic criteria of new daily persistent headache (NDPH) have been revised since 2013. The current review focused on the progress of NDPH research over the last few years. Various new triggers and different NDPH mimics have been reported. The association with both cephalic and extracephalic pathologies suggests that NDPH is rather a syndrome with more than one disease mechanism. Recent clinical studies confirmed that migrainous headache remained the most prominent phenotype of NDPH, echoing the change of the diagnostic criteria in 2013. Diagnostic workup, including imaging studies, was unremarkable, except serving to exclude secondary etiologies. Studies on treatment options have yet shown promising targets, and randomized clinical trials are still lacking. Multiple mechanisms, both cranial and systemic, may be involved synergically in the generation of NDPH-like headaches. The search for effective treatment options should base on better understanding of disease mechanisms.


Advances in Female Germ Cell Induction from Pluripotent Stem Cells.
Germ cells are capable of maintaining species continuity through passing genetic and epigenetic information across generations. Female germ cells mainly develop during the embryonic stage and pass through subsequent developmental stages including primordial germ cells, oogonia, and oocyte. However, due to the limitation of using early human embryos as in vivo research model, in vitro research models are needed to reveal the early developmental process and related mechanisms of female germ cells. After birth, the number of follicles gradually decreases with age. Various conditions which damage ovarian functions would cause premature ovarian failure. Alternative treatments to solve these problems need to be investigated. Germ cell differentiation from pluripotent stem cells in vitro can simulate early embryonic development of female germ cells and clarify unresolved issues during the development process. In addition, pluripotent stem cells could potentially provide promising applications for female fertility preservation after proper in vitro differentiation. Mouse female germ cells have been successfully reconstructed in vitro and delivered to live offspring. However, the derivation of functional human female germ cells has not been fully achieved due to technical limitations and ethical issues. To provide an updated and comprehensive information, this review centers on the major studies on the differentiation of mouse and human female germ cells from pluripotent stem cells and provides references to further studies of developmental mechanisms and potential therapeutic applications of female germ cells.


SS33410, an inhibitor of V-ATPase, blocks intracellular protein transport of the VSV-G protein in the Golgi compartment.
An earlier report suggested that SS33410, structurally related to folimycin and bafilomycin A(1), blocked secretion of the glycoprotein (G protein) of vesicular stomatitis virus (VSV) into the medium and, instead, G protein was accumulated intracellulary. To identify the inhibition site of SS33410 in intracellular protein transport, I have analyzed the oligosaccharide chain structure of the intracellularly accumulated G protein. In SS33410-treated VSV-infected cells, G protein oligosaccharide was suggested to have a composition of GlcNAc-Man(5)-GlcNAc(2) as analyzed by Bio-Gel P-4 column chromatography following digestion with alpha-mannosidase, beta-N-acetylhexosaminidase, and then with alpha-mannosidase. SS33410 specifically inhibited vacuolar-type ATPase (V-ATPase). These studies thus suggest that SS33410 blocks the intracellular protein transport before the step of trimming by mannosidase II, which is confined to the medial Golgi compartment.


[Changing trend of incidence and mortality of stomach cancer during 2010-2016 in Henan Province, China].
Objective: To estimate stomach cancer incidence and mortality in Henan, 2016 and analyze the trend of stomach cancer incidence and mortality from 2010 to 2016. Methods: Stomach cancer related data in 2016 was extracted from Henan cancer registration and follow-up system. All data were qualified in validity, reliability and completeness according to the Guideline on Cancer Registration in China and International Agency for Research on Cancer (IARC/IACR). The incidence and mortality of stomach cancer were estimated by areas, gender and age based on the quality data and the registered population data of Henan province in 2016. The epidemic trend of stomach cancer was also been evaluated based on the age-standardized incidence and mortality by Chinese population (ASR China) from 2010 to 2016. Results: In 2016, the estimated incident cases of stomach cancer were 44 311. The incidence was 41.07/100 000, ASR China was 30.17/100 000, ASR by world population (ASR world) was 30.36/100 000, and the cumulative incidence rate was 3.84%. The incidences of male and female were 55.65/100 000 and 25.35/100 000, respectively. Meanwhile, 32 927 people died of stomach cancer in Henan. The mortality was 30.52/100 000, ASR China was 21.45/100 000, ASR world was 21.54/100 000, and the cumulative mortality was 2.53%. From 2010 to 2016, both the ASR China for incidence and mortality of stomach cancer in Henan showed a steady downward trend. In rural, the ASR China for incidence and mortality decreased rapidly, while the stable trend was observed in urban. Nevertheless, the incidence and mortality of stomach cancer in rural were still higher than those in urban. Conclusions: The incidence and mortality of stomach cancer in Henan province showed steadily declining trend from 2010 to 2016, and the geographical distribution difference between rural and urban areas was gradually narrowing. However, the disease burden was still high in 2016.


Regression of Graft Steatosis After Liver Transplantation.
Introduction: Liver grafts with limited steatosis are currently used for liver transplantation, but the natural history of graft steatosis is not well known. Project Aims or Questions: This program evaluation aimed at assessing changes of steatosis after liver transplantation. Design: A retrospective chart review was performed assessing presence and severity of steatosis in the liver explant and in time zero donor graft biopsies carried out at the time-point of liver transplantation on histopathology and on imaging one year thereafter in 30 well characterized patients. Results: Ten patients (33%) showed steatosis on explant. Time zero biopsy revealed steatosis in 18 grafts (60%) and no steatosis in 12 (40%). One year after transplantation, 8 patients (27%) had steatosis and 22 patients (63%) had none. Fourteen patients (47%) showed changes in steatosis: 12 showed resolution and 2 showed de novo steatosis. Explant macrovesicular steatosis was associated with presence of steatosis 1 year after transplantation (binary logistic regression model, p = 0.014), but not macrovesicular steatosis in the donor graft at time-point of transplantation. Conclusion: Resolution of graft steatosis was frequent. Presence of steatosis in the recipient's liver, but not graft steatosis, was a risk factor for steatosis 1 year after transplantation. Factors related to the recipient seem to prevail over donor-related factors in determining the persistence or de novo appearance of steatosis after liver transplantation.


Cutting edge: lack of peripheral B cells and severe agammaglobulinemia in mice simultaneously lacking Bruton's tyrosine kinase and the B cell-specific transcriptional coactivator OBF-1.
OBF-1 is a B cell-restricted transcriptional coactivator that is recruited to octamer-containing promoters by interacting with the POU domain of Oct-1 or Oct-2. We have shown earlier that mice lacking OBF-1 were dramatically impaired in their ability to mount humoral immune responses and did not develop germinal centers in the spleen; however, they had a largely normal B cell development in the bone marrow. In this study, we demonstrate that OBF-1-deficient mice also have an early defect in B cell development and show that OBF-1-/- immature B cells are greatly impaired at the transition from the bone marrow to the spleen. In addition, when the OBF-1 mutation is combined to a mutation in the gene encoding Bruton's tyrosine kinase, a striking phenotype is observed. These double-deficient animals lack peripheral B cells and have virtually no serum Igs, thus closely resembling human X chromosome-linked agammaglobulinemia.


Seroprevalence study of Tick-borne encephalitis, Borrelia burgdorferi, Dengue and Toscana virus in Turin Province.
Tick borne encephalitis virus (TBEV) is present in some European countries and it is transmitted by a tick bite. Ixodes ricinus is the main vector of the infection in Italy, where fortunately clinical neurological manifestations, typical of the more serious phase of the disease, are very rarely observed. This behaviour is different from other endemic Euroasiatic areas where numerous cases of encephalitis are described. However TBE transmission has not been widely investigated in Italy and available epidemiological data have been obtained only by studies performed in Central and Northern Regions of the country. In addition seroepidemiological researches were made prevalently on subjects at high risk of tick bite, such as hunters or forest guards from Trentin and Central Italy. No precise information about TBE virus diffusion was available in the Piedmont before our investigations. We found that hunters and wild boar breeders seem to be particularly exposed to the risk of TBE virus infection in Turin Province and in particular in the Susa valley, although no neurological involvement was observed in our population. In particular a seroprevalence of about 5% was detected by the use of purified antigens ELISA test, amongst the subjects at high risk of tick bite. Moreover low risk individuals showed a seroprevalence of below 2%. In addition a parallel seroepidemiological study was performed in Turin Province for Borrelia burgdorferi, the aetiological agent of Lyme disease, also transmitted by tick bite (e.g. Ixodes ricinus), for Dengue and Toscana (TOS) arboviruses, respectively transmitted by Aedes mosquitoes and phlebotomes. Data reported here demonstrate only a sporadic presence in our population of antibodies against Borrelia and Dengue infection. Moreover using an ELISA test performed with viral purified nucleoprotein, we reported a total percentage of about 3% of subjects positive for TOSV.


Endophytic Fungi Isolated from Plants Growing in Central Andean Precordillera of Chile with Antifungal Activity against Botrytis cinerea.
Botrytis cinerea is an important phytopathogenic fungus affecting the fruit production around the world. This fungus is controlled mainly by using synthetic fungicides, but many resistant isolates have been selected by the indiscriminate use of fungicides. Endophytic fungi or secondary metabolites obtained from them become an alternative method of control for this fungus. The aim of this work was to identify endophytic fungi with antifungal activity against the plant pathogenic fungus B. cinerea isolated from plants from Central Andean Precordillera of Chile. Three endophytic fungi (Ac1, Lc1 and Ec1) with antifungal activity against B. cinerea were isolated from native and endemic plants growing in Central Andean Precordillera of Chile. The isolates Lc1 (isolated from Lithraea caustica) and Ac1 (isolated from Acacia caven) were identified as Alternaria spp. and the isolate Ec1 (isolated from Echinopsis chiloensis) was identified as Aureobasidium spp. The isolated endophytic fungi would inhibit B. cinerea through the secretion of diffusible and volatile compounds affecting the mycelial growth, conidia germination and interestingly, it was also shown that the volatile compounds produced by the three isolated endophytic fungi suppressed the sporulation of B. cinerea.


Genital tuberculosis can present as disseminated ovarian carcinoma with ascites and raised Ca-125: a case report.
In women with an adnexal mass, ascites and elevated Ca-125 levels, ovarian carcinoma must be ruled out. However, several other conditions, including genital tuberculosis, may present similarly. A 41-year-old woman with weight loss, ascites and elevated levels of Ca-125 was evaluated for ovarian cancer. Computerized tomography revealed an adnexal mass, ascites and lymph nodes on the peritoneal surface. Paracentesis of the ascitic fluid revealed a lymphocytic exudate but failed to show any malignant cells. At laparotomy, frozen sections of tissue biopsies were negative for malignancy; however, a total hysterectomy plus adnexectomy was performed. Postoperatively histologic examination revealed typical features of genital tuberculosis. Antituberculosis treatment was effectively given to the patient. Serum levels of Ca-125 were undetectable 12 weeks after treatment. In conclusion, genital tuberculosis can be misdiagnosed and confused with ovarian cancer. Intraperitoneal tuberculosis should be considered in the differential diagnosis in cases in which ovarian cancer is suspected, even when malignancy-associated risk factors are present.


Cyclic nucleotides in human macrophages: effects of atrial natriuretic factor and nitroprusside on cGMP and cAMP production.
Atrial natriuretic factor (ANF, 10(-7) M) and sodium nitroprusside (SNP, 10(-5)-10(-3) M) stimulated cGMP production in human peritoneal macrophages (HPM). This suggests the existence of two separate forms of guanylate cyclase in HPM, e.g. the receptor-related form by ANF and the soluble form by SNP. In parallel with the rise in cGMP levels, both agents provoked a decrease in cAMP levels. Increasing the concentration of the phosphodiesterase inhibitor IBMX (0.2 mM to 1.0 mM) in the incubation media resulted in a significantly greater rise in cGMP levels which was accompanied by a profound decrease in cAMP levels. ANF did not exert any direct or GTP-related effect on cAMP production, which is in contrast to its action in other tissues. These results suggest that cAMP levels can be modulated through a cGMP signal, most likely at the production level. Results also give substantial evidence for the presence of a ANF receptor site on human peritoneal macrophages.


The importance of being a myoepithelial cell.
The mammary myoepithelial cell was named the 'Cinderella of mammary cell biology' in light of the earlier focus on the luminal cell. Mammary myoepithelial cells have recently been described as 'natural tumour suppressors'. We now need to understand more about their origin and to reconsider their place in the complex process of mammary morphogenesis. In the present review, we discuss the lineage segregation of mammary myoepithelial cells and their functions in mammary gland development. These functions include their effects on luminal cell growth and differentiation, their key role in the establishment of the polarised mammary epithelial bilayer and the control of stromal invasion in breast cancer.


Interstitial lung disease and myositis in a patient with simultaneously occurring sarcoidosis and scleroderma.
A patient initially presented with sarcoidosis in combination with myositis of sarcoid origin and Raynaud's phenomenon. During the course of his disease, he additionally developed scleroderma. Bronchoalveolar lavage, performed because of increase of interstitial markings in the presence of enlarged hilar nodes, showed an increased percentage of granulocytes and a low CD4 to CD8 ratio of lymphocytes, suggesting a change to scleroderma lung disease.


Amination of polystyrene microwells: application to the covalent grafting of DNA probes for hybridization assays.
Amine functionalization of polystyrene microwells for covalent binding of DNA is described. Polystyrene support was first carboxylated by permanganate oxidation in diluted sulfuric acid. These functions were activated with water-soluble carbodiimide and grafted with N-methyl-1,3-propane diamine to introduce a free secondary amino group on the support. The samples were characterized by X-ray photoelectron spectroscopy and radiochemical assay. The conditions for covalent linkage of secondary amine on polystyrene microwells were optimized. Functionalized supports were used for covalent binding of a DNA capture probe for the detection of human cytomegalovirus in a sandwich hybridization assay. Sensitivity of the assay compared very well with a commercially available surface, Covalink-NH, microwell plate obtained by electromagnetic irradiation.


Estimating the prevalence of hepatitis C infection in New York City using surveillance data.
Hepatitis C virus is the most common chronic blood-borne infection in the USA. Based on results of a serosurvey, national prevalence is estimated to be 1·3% or 3·2 million people. Sub-national estimates are not available for most jurisdictions. Hepatitis C surveillance data was adjusted for death, out-migration, under-diagnosis, and undetectable blood RNA, to estimate prevalence in New York City (NYC). The prevalence of hepatitis C infection in adults aged ⩾20 years in NYC is 2·37% (range 1·53-4·90%) or 146 500 cases of hepatitis C. This analysis presents a mechanism for generating prevalence estimates using local surveillance data accounting for biases and difficulty in accessing hard to reach populations. As the cohort of patients with hepatitis C age and require additional medical care, local public health officials will need a method to generate prevalence estimates to allocate resources. This approach can serve as a guideline for generating local estimates using surveillance data that is less resource prohibitive.


Enhancement of 1.53 μm emission in erbium/cerium-doped germanosilicate glass pumped by common 808 nm laser diode.
Erbium-doped germanosilicate glasses with various cerium ions contents have been prepared. Optical absorption and 1.53 μm emission spectra were measured to characterize the spectroscopic performances of prepared samples. A detailed study of 1.53 μm spectroscopic properties was carried out when pumped by an 808 nm laser diode. Moreover, an energy level diagram and an energy transfer mechanism between Er3+ and Ce3+ were proposed to elucidate the enhanced 1.53 μm fluorescence. It is found that the prepared samples have optimal spectroscopic properties when the Ce3+ concentration is fixed to 0.5 mol. %. High spontaneous radiative transition probability (172.66 s(-1)), large effective emission bandwidth (74 nm), and emission cross section (9.49×10(-21) cm(2) indicate that 808 nm pumped Er3+/Ce3+ codoped germanosilicate glass might be a suitable material for a broadband optical amplifier.


Metabolic engineering of Bacillus subtilis for chiral pure meso-2,3-butanediol production.
2,3-Butanediol (2,3-BD) with low toxicity to microbes, could be a promising alternative for biofuel production. However, most of the 2,3-BD producers are opportunistic pathogens that are not suitable for industrial-scale fermentation. In our previous study, wild-type Bacillus subtilis 168, as a class I microorganism, was first found to generate only d-(-)-2,3-BD (purity >99 %) under low oxygen conditions. In this work, B. subtilis was engineered to produce chiral pure meso-2,3-BD. First, d-(-)-2,3-BD production was abolished by deleting d-(-)-2,3-BD dehydrogenase coding gene bdhA, and acoA gene was knocked out to prevent the degradation of acetoin (AC), the immediate precursor of 2,3-BD. Next, both pta and ldh gene were deleted to decrease the accumulation of the byproducts, acetate and l-lactate. We further introduced the meso-2,3-BD dehydrogenase coding gene budC from Klebsiella pneumoniae CICC10011, as well as overexpressed alsSD in the tetra-mutant (ΔacoAΔbdhAΔptaΔldh) to achieve the efficient production of chiral meso-2,3-BD. Finally, the pool of NADH availability was further increased to facilitate the conversion of meso-2,3-BD from AC by overexpressing udhA gene (coding a soluble transhydrogenase) and low dissolved oxygen control during the cultivation. Under microaerobic oxygen conditions, the best strain BSF9 produced 103.7 g/L meso-2,3-BD with a yield of 0.487 g/g glucose in the 5-L batch fermenter, and the titer of the main byproduct AC was no more than 1.1 g/L. This work offered a novel strategy for the production of chiral pure meso-2,3-BD in B. subtilis. To our knowledge, this is the first report indicating that metabolic engineered B. subtilis could produce chiral meso-2,3-BD with high purity under limited oxygen conditions. These results further demonstrated that B. subtilis as a class I microorganism is a competitive industrial-level meso-2,3-BD producer.


Texture formation in carbonaceous mesophase fibers.
Carbonaceous mesophases are discotic nematic liquid crystals that are spun into high performance carbon fibers using the melt spinning process. The spinning process produces a wide range of different fiber textures. Planar polar (PP) and planar radial (PR) textures are two ubiquitous ones. This paper presents theory and simulation of the texture formation process using the Landau-de Gennes mesoscopic theory for discotic liquid crystals. The computed PP and PR textures phase diagram, given in terms of temperature and fiber radius, is presented to establish the processing conditions and geometric factors that lead to the selection of these textures. Thin fibers adopt the PR texture, while thicker fibers and higher temperatures adopt the PP texture. The influence of elastic anisotropy to the formation of textures and structure is thoroughly characterized.


Prioritizing Targets and Minimizing Distraction Within Limited Capacity Working Memory: Commentary on 'Working memory and attention; a conceptual analysis and review' by Klaus Oberauer.
Oberauer (2019) maps out different perspectives that have emerged in exploring working memory and attention, and suggests particular ways in which these key aspects of cognition might operate in the service of successful goal completion. One question that is central to Oberauer's review and to the field more generally concerns how automatic and controlled attention interact with each other and with working memory. In line with this, recent research indicates that both forms of attention can operate within the same task to determine whether information is maintained in working memory. Perceptual attention can be automatically captured by environmental input, resulting in superior recall for the most recent stimulus, along with unwanted disruption by distracting stimuli. Effortful top-down control, powered by executive resources, operates within this context to create and maintain task goals, and to support the maintenance of target information in an accessible state, particularly if it is of greater value/goal relevance.


Evidence for a Possible Link between Bedtime and Change in Body Mass Index.
The aim of the current study was to examine the longitudinal relationship between bedtimes and body mass index (BMI) from adolescence to adulthood in a nationally representative sample. Three waves of data from the National Longitudinal Study of Adolescent Health were used to assess the bedtimes and BMI of 3,342 adolescents between 1994 and 2009. Hypotheses were tested with hierarchical linear models using a two-level, random intercept and slopes model. Later average bedtime during the workweek, in hours, from adolescence to adulthood was associated with an increase in BMI over time (b = 0.035 kg/m(2) per min later bedtime per 6 years; standard error = 0.016; t = 2.12, degrees of freedom = 3,238, P < 0.05). These results remained significant after controlling for demographic characteristics and baseline BMI. Although sleep duration, screen time, and exercise frequency did not attenuate the relationship between workday bedtime and BMI over time, fast-food consumption was recognized as a significant partial mediator of the relationship between bedtimes and BMI longitudinally. The results highlight bedtimes as a potential target for weight management during adolescence and during the transition to adulthood.


Cervical lung lobe herniation in dogs identified by fluoroscopy.
This study aimed to determine the frequency of cervical lung lobe herniation (CLLH) in dogs evaluated fluoroscopically and to identify associated characteristics. Reports of diagnostic procedures and patient summaries from 2008 to 2010 were reviewed retrospectively. Signalment, body weight, duration of cough, presence of heart murmur and airway collapse, and radiographic findings were compared between dogs with and without CLLH. Of the 121 dogs that were examined, CLLH occurred in 85 (70%). The extra-thoracic trachea kinked during herniation in 33 (39%) dogs with CLLH. Collapse of the intra-thoracic trachea (assessed fluoroscopically or bronchoscopically) and collapse of major bronchi (assessed fluoroscopically) were strongly associated with CLLH. Although redundant dorsal tracheal membrane on radiographs was associated with CLLH, extra-thoracic tracheal collapse, assessed fluoroscopically or bronchoscopically, was not. No other associations were found. Cervical lung lobe herniation was present in most dogs evaluated during cough and was associated with intra-thoracic large airway collapse, but not duration of cough.


[BRG1 expression in prostate carcinoma by application of tissue microarray].
To investigate the expression of gene BRG1 in prostatic intraepithelial neoplasia and adenocarcinoma, and the relationship between gene BRG1 expression and the clinicopathological features of prostate carcinoma. Gene BRG1 expression was evaluated in 37 cases of human prostate carcinoma, 13 human prostatic intraepithelial neoplasia (PIN) and 14 human benign prostatic hyperplasia (BPH) by using immunohistochemistry (EnVision method) and tissue microarray. The positive rates of BRG1 protein were 81.08% (30/37), 38.46% (5/13) and 14.28% (2/14) in prostate carcinoma, PIN and BPH, respectively, significantly higher in the first group than in the latter two (P < 0.05). There was no statistically significant difference in BRG1 gene expression either between PIN and BPH (P > 0.05) or between the groups of the moderate differentiation (the Gleason histologic grading: 5-7) and the lower one (the Gleason histologic grading: 8-10) (P > 0.05). BRG1 may play an important role in the development of prostate carcinoma. Tissue microarray technology, with the advantages of high throughput, conciseness, rapidity, high efficiency, low cost, and nice reproducibility, has significant practical value and broad application prospects in pathology.


Cowper's syringocele: an analysis of 15 consecutive cases.
Cystic dilatation of Cowper's gland ducts (Cowper's syringocele) is uncommon in children and is frequently asymptomatic, but it may cause urinary infection, haematuria, dysuria, and obstructive voiding symptoms. Fifteen consecutive children with syringocele aged 15 days to 15 years old are reported here. Only four patients with obstructive syringocele were successfully treated surgically; all the others were successfully treated conservatively. The true clinical significance of Cowper's syringocele lies in its potential to cause urethral obstruction. Careful clinical, radiological, endoscopic, and urodynamic evaluation is necessary in order to avoid unnecessary surgery.


Analysis of the Rhodobacter capsulatus puc operon: the pucC gene plays a central role in the regulation of LHII (B800-850 complex) expression.
Formation of the light harvesting complex B800-850 (LHII) of Rhodobacter capsulatus requires the expression of more than the three known genes specific for that complex (pucA, pucB and pucE) encoding the alpha, beta and gamma subunits of LHII, respectively. In this work evidence is presented that the product of the gene pucC, which is located downstream from pucA, is essential for high-level transcription of the pucBACDE operon and formation of LHII. Plasmids were constructed containing deletions in one or several puc genes and transferred to a pucC::Tn5 mutant in which the puc operon is not expressed. It was found that the LHII- phenotype of the mutant was due to the missing PucC protein and that all known puc genes are located in one operon. To dissect the pucC, pucD and pucE genes from pucB and pucA and independently regulate them, they were placed under control of the nifHDK promoter. Only under nitrogen-fixing growth conditions was the LHII- pucC::Tn5 mutant complemented by this construction. It is concluded that expression of pucC is essential for formation of the LHII complex in R.capsulatus. Analysis of the pucD and pucE genes led to the conclusion that the products of these genes stabilize the B800-850 complex.


Comparative analysis of completed parity distributions: a global WFS perspective.
This paper studies completed parity distributions for all the industrialized and developing countries that participated in the World Fertility Survey. This is done by means of a table based on parity calculated for all ever-married women above age 40 by educational and residential subcategories. The information is also used to compare mean family and mean sibship sizes and to study changes in the concentration of reproduction independent of the level of fertility. The cross- section of countries considered implies that, as fertility declines, the transition from high to low fertility is associated with an increase in the concentration; i.e., a smaller proportion of women having 1/2 the children. The big exception is China, where fertility declined steeply without an increase in concentration.


Aberrant tubulointerstitial immunoexpression of matrix metalloproteinases MMP-2, MMP-9 and tissue inhibitor of matrix proteinase-2 (TIMP-2) in acute cellular rejection of human renal allograft.
Acute cellular rejection (ACR) may initiate chronic allograft dysfunction with alterations in the extracellular matrix compartment (ECM). Turnover of ECM proteins is regulated by matrix metalloproteinases (MMPs). The aim of the present study was to determine the immunoexpression of MMP-2, MMP-9 and TIMP-2 in ACR, and to examine the relationship between expression of MMPs and monocytes/macrophages, transforming growth factor beta-1 (TGFbeta-1), and alpha-smooth muscle actin (alpha-SMA). Immunoperoxidase study with antibodies against MMP-2, MMP-9, TIMP-2, CD68, TGFbeta-1 and alpha-SMA was carried out on 24 renal allograft biopsy specimens from patients with ACR and 11 allograft biopsy specimens from patients with no signs of rejection. Our study revealed increased immunoexpression of MMP-2, MMP-9 and TIM-2 in ACR as compared with controls, and significant positive correlations between immunostaining of MMP-2 and TGF-beta-1, as well as between MMP-2 and alpha-SMA. Increased immunoexpression of MMP-9 was positively correlated with alpha-SMA, and the number of interstitial CD68+cells. In conclusion our study supports a role of gelatinases in tissue damage in human renal acute cellular allograft rejection and provides some interesting insights into early renal remodeling which may lead to chronic allograft dysfunction.


The Effect of Time During the Academic Year or Resident Training Level on Complication Rates After Lower-Extremity Orthopaedic Trauma Procedures.
Few studies have evaluated the effect of resident participation on morbidity and mortality after orthopaedic trauma surgery. The goal of this study was to evaluate whether complications after orthopaedic trauma procedures involving residents correlate with the level of resident training and the timing in the academic year. The American College of Surgeons National Surgical Quality Improvement Program database was queried for all patients who underwent operative fixation of proximal femoral fractures, femoral shaft fractures, and tibial shaft fractures from 2005 to 2012. A total of 1,851 cases with resident involvement were identified, and complication rates were calculated and analyzed with respect to resident level of training (postgraduate year [PGY] 1 through 6) and the academic quarter in which the procedure took place. The composite complication rates in the first academic quarter for serious adverse events (10.96%), any adverse events (18.57%), and surgical complications (9.62%) did not significantly differ from those during the remainder of the year (11.40%, 17.81%, and 7.19%, respectively). The rates of any adverse event were significantly higher for senior-level residents (quarter 1, 20.58%; quarter 2, 20.05%) than for junior residents (quarter 1, 11.76%; quarter 2, 12.44%) during the first half of the academic year (quarter 1, p = 0.044; quarter 2, p = 0.024). This evaluation of the composite complication rates found no "July effect" in lower-extremity orthopaedic trauma surgery. There was evidence for a July effect for superficial surgical site infections, in that there was a significantly higher rate in the first academic quarter. Senior residents may benefit from more oversight or instruction during the first portion of the academic year.


Phase transitions in thylakoid polar lipids of chilling-sensitive plants: a comparison of detection methods.
The phase behavior of thylakoid polar lipids from plants sensitive to chilling injury was investigated by calorimetry, electron spin resonance spectroscopy of spin labels, and fluorescence intensity after labeling with trans-parinaric acid. The plants used were oleander (Nerium oleander), mung bean (Vigna radiata L. var Mungo), and tomato (Lycopersicon esculentum cv Grosse Lisse). For all plants the initiation temperature for the calorimetric exotherm was coincident (+/-1 degrees C) with the transition determined by the increase in the temperature coefficient of spin label motion and fluorescence intensity of trans-parinaric acid. For oleander plants, grown at 45 degrees C, the transition was at 7 degrees C while for plants from the same clone, grown at 20 degrees C, it was at -2 degrees C. For mung bean and tomato the transition was between 9 and 12 degrees C. The similarity in the transition detected by spin labeling and fluorescence intensity suggest that spin labels, like the fluorescent label trans-parinaric acid, preferentially partition into domains of ordered lipid. The coincidence of the temperature for initiation of the transition, determined by the three techniques, shows that each is a valid method of assessing a phase transition in membrane polar lipids.


Valid Post-clustering Differential Analysis for Single-Cell RNA-Seq.
Single-cell computational pipelines involve two critical steps: organizing cells (clustering) and identifying the markers driving this organization (differential expression analysis). State-of-the-art pipelines perform differential analysis after clustering on the same dataset. We observe that because clustering "forces" separation, reusing the same dataset generates artificially low p values and hence false discoveries. We introduce a valid post-clustering differential analysis framework, which corrects for this problem. We provide software at https://github.com/jessemzhang/tn_test.


Use of emollients in dry skin conditions.
As nurses receive inadequate training in dermatology, they may lack knowledge in prescribing and using emollients. This article outlines the physiology of the skin, the role of emollient therapy and how to use it in clinical practice.


Quantitative radiomic model for predicting malignancy of small solid pulmonary nodules detected by low-dose CT screening.
It is a permanent challenge to differentiate small solid lung nodules. Massive data, extracted from medical image through radiomics analysis, may help early diagnosis of lung cancer. The aim of this study was to assess the usefulness of a quantitative radiomic model developed from baseline low-dose computed tomography (LDCT) screening for the purpose of predicting malignancy in small solid pulmonary nodules (SSPNs). This retrospective study included malignant and benign SSPNs (6 to 15 mm) detected in baseline low-dose CT screening. The malignancy was confirmed pathologically, and benignity was confirmed by long term follow-up or pathological diagnosis. The non-contrast CT images were reconstructed with a lung kernel of a slice thickness of 1 mm and were processed to extract 385 quantitative radiomic features using Analysis-Kinetic software. A predictive model was established with the training set of 156 benign and 40 malignant nodules, and was tested with the validation set of 77 benign and 21 malignant nodules through the analysis of R square. The performance of the radiomic model in predicting malignancy was compared with that of the ACR Lung Imaging Reporting and Data System (ACR lung-RADS). In 294 cases of SSPNs, 61 lung cancers and 24 benign nodules were confirmed pathologically and the remaining 209 nodules were stable with long-term follow-up (4.1±0.9 years). Eleven non-redundant features, including 8 high-order texture features, were extracted from the training data set. The sensitivity and specificity of the prediction model in malignancy differentiation were 81.0% and 92.2% respectively. The accuracy was superior to ACR-lung RADS (89.8% vs. 76.5%). A radiomic model based on baseline low-dose CT screening for lung cancer can improve the accuracy in predicting malignancy of SSPNs.


Cytoarchitectural findings in the diagnosis of primary soft tissue tumors.
To review the major cytologic and architectural criteria in the diagnosis of primary soft tissue tumors, highlighting the importance of clinical correlation and the value of ancillary methods. Given the variety and complexity of clinicopathologic entities, the initial approach is based on pattern analysis. Six basic categories are established as a function of cell shape, stromal characteristics and resemblance to normal tissue. First, in myxoid-rich matrix tumors, special attention should be paid to lipoblasts, ganglion type, stellate cells and metachromatic fibrillar matrix. Second, in round cell tumors the following cytoarchitectural findings are of special interest: atypical rhabdomyoblasts, atypical lipoblasts, neuroblast rosettes, cytoplasmic glycogen, melanin pigment, islets of mature cartilage, hyaline cytoplasmic inclusions and fragments of connective tissue closely associated with round cells. Third, in spindle tumors the most important cytoarchitectural findings are: biphasic cellularity; elongated, buckled or wavy, tapered nuclei; nuclear palisades; straight, elongated, blunt-ended nuclei; melanotic pigment; storiform pattern; tissue fragments with collagen fibers or degenerated elastin; intracytoplasmic hyaline globules; and scattered spindle cells in a background of red blood cells. Fourth, in pleomorphic tumors specific typing is often difficult, if not impossible, since cells display few or no differential features. Fifth, in epithelial like cell tumors the cytologic findings of major diagnostic interest are: melanin deposits, crystalline inclusions, intracytoplasmic lumina, anisonucleosis and nuclear cytoplasmic inclusions. Last, in maturelike cell tumors, the architectural pattern resembles that of mature tissues. Although cytologic analysis of primary soft tissue tumors is hampered by the paucity of diagnostic findings, the establishment of clinicocytologic correlations, taking into account architectural patterns, cytologic details and clinical characteristics of the lesion, allows precise diagnosis of a significant number of tumors. Application of new techniques (immunocytochemistry, electron microscopy and cytogenetics) to cytologic aspirates has prompted a substantial reduction in the number of doubtful clinicocytologic diagnoses and considerably broadened the diagnostic spectrum.


Vacuum-sealed specimen stage for scanning microscopy of air-sensitive materials.
A vacuum-sealed specimen stage for investigation of air-sensitive materials has been designed. This stage is useful for instruments equipped with a vacuum antechamber and allows facile sample mounting in a dry box or glove bag. The sample cell is subsequently introduced into the antechamber of the instrument and the appropriate measurement or photograph is taken. Sample integrity can be maintained in the cell for subsequent investigations.


Overlapping distribution of receptors for atrial natriuretic peptide and angiotensin II in the kidney and the adrenal gland of the freshwater turtle, Amyda japonica.
The distribution of receptors for atrial natriuretic peptide (ANP) and angiotensin II (ANG II) in the kidney and adrenal gland of the freshwater turtle, Amyda japonica, was examined by quantitative in vitro autoradiography using 125I-labeled rat (r)ANP1-28 and 125I-labeled human ANG II as labeled ligands. Receptor subtypes were characterized by competition with des[Gln18,Ser19,Gly20, Leu21, Gly22] ANP(4-23) (C-ANP) as a selective ligand of the clearance receptors to specific 125I-rANP(1-28) binding, and with DuP 753 and PD 123319 as nonpeptide antagonists for ANG II receptors type 1 (AT1) and type 2 (AT2) subtypes, respectively, to 125I-ANG II binding. Specific 125I-rANP(1-28) binding with a single binding site was found overlying glomeruli of the kidney and the outer zone of the adrenal gland with dissociation constants (Kd) of 4.39 +/- 0.33 and 6.07 +/- 1.36 nM, respectively. C-ANP (10 microM) inhibited about 90% of the glomerular and adrenal 125I-rANP(1-28) binding. Specific 125I-ANG II binding was also localized in the glomeruli of the kidney and the outer zone of the adrenal gland with Kd of 1.02 +/- 0.22 and 0.37 +/- 0.04 nM, respectively. DuP 753 (10 microM) potently inhibited about 80% of glomerular and 90% of adrenal 125I-ANG II binding, whereas PD 123319 (10 microM) was very weak in competing for specific 125I-ANG II binding in both tissues. Therefore, these results indicate that specific ANP and ANG II receptors with high affinities have an overlapping distribution in glomeruli of the kidney and the outer zone of the adrenal gland of the freshwater turtle. They also suggest that biological and clearance ANP receptor-like subtypes coexist in both tissues, and the predominant ANG II receptor subtype in these tissues is the AT1-like receptor. The overlapping distribution of specific receptors for both peptides in these tissues provides the basis for possible receptor interactions to exert a functional antagonism between ANP and ANG II in the freshwater turtle.


Mental Health Practitioners' Understanding of Speech Pathology in a Regional Australian Community.
(1) Background: This study aimed to determine the level of knowledge and the perceptions of speech pathology held by a sample of regional mental health practitioners and to explore factors that facilitate understanding of the roles of speech pathologists in mental health. While mental health is recognised as an area of practice by Speech Pathology Australia, the inclusion of speech pathologists in mental health teams is limited. (2) Methods: An anonymous online survey was created using previously validated surveys and author generated questions and distributed to mental health practitioners in Central Queensland, Australia. (3) Results: Mental health practitioners had difficulty identifying speech pathology involvement when presented with case scenarios. Accuracy was poor for language-based cases, ranging from 28.81% to 37.29%. Participants who reported having worked with a speech pathologist were more likely to demonstrate higher scores on the areas of practice questions, [r(53) = 0.301, p = 0.028], and the language scenarios [r(58) = 0.506, p < 0.001]. They were also more likely to agree to statements regarding the connection between speech pathology and mental health, r(59) = 0.527, p < 0.001. (4) Conclusions: As found in this study, contact with speech pathologists is a strong predictor of mental health providers' knowledge of the speech pathology profession. Thus, the challenge may be to increase this contact with mental health providers to promote inclusion of speech pathologists in the mental health domain.


Gelatine Film Incorporated with Clitoria ternatea-Derived Anthocyanin Microcapsules, A Food Packaging Material Effective Against Foodborne Pathogens.
Microbial contamination of food products is one of the significant causes of food spoilage and foodborne illnesses. The use of active packaging films incorporated with antimicrobial agents can be a measure to improve food quality and extend shelf life. Nevertheless, antimicrobial agents such as silver, copper, titanium and zinc in the packaging films have raised concerns among consumers due to toxicity issues. The current study aims to develop biodegradable gelatine-based edible films incorporated with microcapsules of Clitoria ternatea-derived anthocyanins as a natural antimicrobial agent. The impact of incorporation of microcapsules with anthocyanins on the morphology, thermal, mechanical, water vapour barrier and physicochemical properties of the gelatine films was evaluated in this study. The effectiveness of the developed films against foodborne pathogens and their application for perishable food protection were also investigated. The results show that incorporating anthocyanin microcapsules enhances the gelatine film physical and mechanical properties by increasing the thickness, tensile strength, Young's modulus and elongation at break of the films. Scanning electronic microscopy analysis revealed that the film surface morphology with anthocyanin microcapsules had a homogeneous and smooth surface texture compared to the control. The thermogravimetric analysis also showed a slight improvement in the thermal properties of the developed films. Agar well diffusion assay revealed that the developed films exhibit significant inhibition against a broad-spectrum of bacteria. Furthermore, the films composed of gelatine with anthocyanin microcapsules significantly reduced the total viable count of microorganisms in the bean curd during storage for 12 days compared with the control films. Increasing global awareness of healthy and safe food with minimal synthetic ingredients as preservatives has sparked the search for the use of antimicrobial agents of natural origins in active food packaging material. In this study, a safe and effective active packaging film was developed using an environmentally friendly biopolymer, gelatine film incorporated with microcapsules of Clitoria ternatea-derived anthocyanins as a natural antimicrobial agent. This study demonstrated that such a method is not only able to improve the film physical properties but can also significantly prolong the shelf life of food products by protecting them from microbial spoilage.


Changes in life-quality, a possible symptom of dementia development.
Dementia is a chronic and irreversible brain impairment characterised by significant cognitive deficits. Severe symptoms of the aforesaid disease interfere with normal life functions and daily activities. Dementia usually develops with advancing age, i.e. after the age of 85, and when it develops in people younger than age 65, it is referred to as early onset dementia. This paper presents a 53-year-old male patient. Provisional diagnosis was established while further diagnostic workup included psycho-diagnostic assessment, neurological exam, and brain CT Such workup confirmed the development of dementia, i.e. early-onset Alzheimer's disease accompanied by depressed mood with impaired vision.


Quality of life of immigrants and nonimmigrants in psychiatric rehabilitation.
Objective: This study examined whether personal characteristics of consumers with serious mental illness (SMI), including being an immigrant, explained the lack of concordance in quality-of-life (QOL) ratings reported by consumers versus those reported by staff caring for consumers. Method: In a sample of consumers with SMI (n = 4,956), including nonimmigrants and immigrants from Ethiopia and countries comprising the former Soviet Union (FSU), we examined consumer-reported and staff-reported QOL ratings. Regression models measured the contributions of covariates to QOL ratings made by both groups. Results: Staff-reported QOL ratings were consistently lower than consumer-reported QOL ratings. Consumer-reported QOL ratings made by FSU immigrants were lower than consumer-reported QOL ratings made by Ethiopian immigrants or by nonimmigrants (p < .01). Conversely, staff-reported QOL ratings on Ethiopian immigrants were lower than staff-reported QOL ratings on FSU immigrants or nonimmigrants (p < .05). While consumer-reported QOL ratings were associated with the covariates of gender (p < .01), disability level (p < .001), and health status (p < .001), staff-reported QOL ratings were associated with the covariates of single marital status (p < .05), education (p < .001), and disability level (p < .001). Conclusions and Implications for Practice: Among consumers with SMI, FSU immigrants reported the lowest QOL ratings, yet staff rated the QOL of Ethiopian immigrants as the lowest. Bias is a potential explanation for this discrepancy. An educational program focusing on cultural awareness, sensitivity, and competency might help staff better understand consumers' needs, thereby contributing to better service and potentially improving staff's ability to make assessments of consumers' functioning and QOL. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


The Osteocyte Stimulated by Wnt Agonist SKL2001 Is a Safe Osteogenic Niche Improving Bioactivities in a Polycaprolactone and Cell Integrated 3D Module.
Finding and constructing an osteogenic microenvironment similar to natural bone tissue has always been a frontier topic in orthopedics. We found that osteocytes are targeting cells controlling bone anabolism produced by PTH (JBMR 2017, PMID: 27704638), and osteocytes with activated Wnt signaling orchestrate bone formation and resorption (PNAS 2015, PMID: 25605937). However, methods for taking advantage of the leading role of osteocytes in bone regeneration remain unexplored. Herein, we found that the osteocytes with SKL2001-activated Wnt signaling could be an osteogenic microenvironment (SOOME) which upregulates the expression of bone transcription factor Runx2 and Bglap and promotes the differentiation of bone marrow stromal cell ST2 into osteoblasts. Interestingly, 60 μM SKL2001 treatment of osteocytic MLO-Y4 for 24 h maintained Wnt signaling activation for three days after removal, which was sufficient to induce osteoblast differentiation. Triptonide, a Wnt inhibitor, could eliminate this differentiation. Moreover, on day 5, the Wnt signaling naturally decreased to the level of the control group, indicating that this method of Wnt-signaling induction is safe to use. We quickly verified in vivo function of SOOME to a good proximation in 3D bioprinted modules composed of reciprocally printed polycaprolactone bundles (for support) and cell bundles (for bioactivity). In the cell bundles, SOOME stably supported the growth and development of ST2 cells, the 7-day survival rate was as high as 91.6%, and proliferation ability increased linearly. Similarly, SOOME greatly promoted ST2 differentiation and mineralization for 28 days. In addition, SOOME upregulated the expression of angiopoietin 1, promoted endothelial cell migration and angiogenesis, and increased node number and total length of tubes and branches. Finally, we found that the function of SOOME could be realized through the paracrine pathway. This study reveals that osteocytes with Wnt signaling activated by SKL2001 are a safe osteogenic microenvironment. Both SOOME itself and its cell-free culture supernatant can improve bioactivity for osteoblast differentiation, with composite scaffolds especially bearing application value.


[Determination of fluorine-ion in human urine by ion chromatography method].
Objective: To establish a method to determine fluorine ion in human urine by ion chromatography method. Methods: The samples were centrifuged, diluted and processed by C(18) solid-phase column, potassium hydroxide as mobile phase, gradient elution, separated by AS(15), and determined by anion conductivity detector. Results: The linear correlation coefficient of fluoride ion in the range of 0.02-10.00 mg/L was more than 0.999. The lowest detection limit of urinary fluoride was 0.06 mg/L (in 3 ml urine) . The recoveries of the method were 96.9%-99.5%, the inter batch precision range was 0.40%-2.89%. The intra batch precision was from 1.01 to 7.23%. Fluoride samples could be stored for 7 days at room temperature and 4 ℃, and be stored for 14 days at -20 ℃. Conclusion: Determination of fluoride in urine by ion chromatography, the method could meet the requirement in GBZ/T 210.5-2008.


Proteomic analysis of renal calculi indicates an important role for inflammatory processes in calcium stone formation.
Even though renal stones/calculi occur in approximately 10% of individuals, they are an enormous economic burden to the entire US health system. While the relative metabolic composition of renal calculi is generally known, there is no clear understanding of the genetics of renal stone formation, nor are there clear prognostic indicators of renal stone formation. The application of proteomics to the analysis of renal calculi axiomatically holds that insight into renal stone pathobiology can be gained by a more comprehensive understanding of renal calculus protein composition. We analyzed isolated renal stone matrix proteins with mass spectrometric and immunohistochemical methods identifying 158 proteins with high confidence, including 28 common proteins. The abundant proteins included those identified previously in stones and proteins identified here for the first time, such as myeloid lineage-specific, integral membrane and lipid regulatory proteins. Pathway analyses of all proteins identified suggested that a significant fraction of the most abundant matrix proteins participate in inflammatory processes. These proteomic results support the hypothesis that stone formation induces a cellular inflammatory response and the protein components of this response contribute to the abundant stone matrix proteome.


Prevalence of the crayfish plague pathogen Aphanomyces astaci in populations of the signal crayfish Pacifastacus leniusculus in France: evaluating the threat to native crayfish.
Aphanomyces astaci, the crayfish plague pathogen, first appeared in Europe in the mid-19(th) century and is still responsible for mass mortalities of native European crayfish. The spread of this parasite across the continent is especially facilitated by invasive North American crayfish species that serve as its reservoir. In France, multiple cases of native crayfish mortalities have been suggested to be connected with the presence of the signal crayfish Pacifastacus leniusculus, which is highly abundant in the country. It shares similar habitats as the native white-clawed crayfish Austropotamobius pallipes and, when infected, the signal crayfish might therefore easily transmit the pathogen to the native species. We investigated the prevalence of A. astaci in French signal crayfish populations to evaluate the danger they represent to local populations of native crayfish. Over 500 individuals of Pacifastacus leniusculus from 45 French populations were analysed, plus several additional individuals of other non-indigenous crayfish species Orconectes limosus, O. immunis and Procambarus clarkii. Altogether, 20% of analysed signal crayfish tested positive for Aphanomyces astaci, and the pathogen was detected in more than half of the studied populations. Local prevalence varied significantly, ranging from 0% up to 80%, but wide confidence intervals suggest that the number of populations infected by A. astaci may be even higher than our results show. Analysis of several individuals of other introduced species revealed infections among two of these, O. immunis and P. clarkii. Our results confirm that the widespread signal crayfish serves as a key reservoir of Aphanomyces astaci in France and therefore represents a serious danger to native crayfish species, especially the white-clawed crayfish. The prevalence in other non-indigenous crayfish should also be investigated as they likely contribute to pathogen transmission in the country.


Some features of the developmental uterus in human fetuses.
Proper development of each component of the reproductive tract is imperative for successful natural reproduction. The aim was to investigate some morphological features of the fetal uterus in early phases of its development. The uteruses of 65 fetuses of different gestational age were included and each of them was measured in three dimensions: uterine length (UL), uterine width (BC) and the antero-posterior (sagittal) thickness of the uterine fundus (FT) using ImageJ computer program. It was observed that the most intense fetal uterus growth occurred between seventh and eighth month of gestational age (between week 25 and 31). The most intense rate of uterine growth had UL and it showed steeper growth curve from the fourth month of gestational age. The values of UL, BC, FT showed statistically highly positive Pearson's linear correlation with values of CRL, and GA, and among themselves. The strongest correlation was between UL and gestational age. Contrary to proved rising linear trends of UL/FT and UL/BC, BC/FT performed linear trend of decline. However, two divergent linear trends, one ascending (UL/FT), and other declining (BC/FT) have similar descent in values during the early gestational age, from week 12 to 15. Fetal uteruses did not grow at the same rate by all three measured dimensions, and each of measured dimensions has noticeable standard deviations during gestational periods, even with a resolution of a week, suggesting individuality of each human development/growth even during prenatal life.


Bonding of a resin-modified glass ionomer cement to dentin using universal adhesives.
This study aims to assess the effect of universal adhesives pretreatment on the bond strength of resin-modified glass ionomer cement to dentin. Fifty caries-free human third molars were employed. The teeth were randomly assigned into five groups (n = 10) based on dentin surface pretreatments: Single Bond Universal (3M Oral Care), Gluma Bond Universal (Heraeus Kulzer), Prime&Bond Elect (Dentsply), Cavity Conditioner (GC) and control (no surface treatment). After Fuji II LC (GC) was bonded to the dentin surfaces, the specimens were stored for 7 days at 37°C. The specimens were segmented into microspecimens, and the microspecimens were subjugated to microtensile bond strength testing (1.0 mm/min). The modes of failure analyzed using a stereomicroscope and scanning electron microscopy. Data were statistically analyzed with one-way analysis of variance and Duncan tests (p = 0.05). The surface pretreatments with the universal adhesives and conditioner increased the bond strength of Fuji II LC to dentin (p < 0.05). Single Bond Universal and Gluma Bond Universal provided higher bond strength to Fuji II LC than Cavity Conditioner (p < 0.05). The bond strengths obtained from Prime&Bond Elect and Cavity Conditioner were not statistically different (p > 0.05). The universal adhesives and polyacrylic acid conditioner could increase the bond strength of resin-modified glass ionomer cement (RMGIC) to dentin. The use of universal adhesives before the application of RMGIC may be more beneficial in improving bond strength.


Hedgehog signaling: new targets for GPCRs coupled to cAMP and protein kinase A.
Hedgehog (HH) is a secreted protein named for the bristle phenotype observed in Drosophila embryos that lack the corresponding gene. Three homologs have been characterized in vertebrates, all which have critical roles in the development of multiple organ systems. Moreover, these proteins regulate stem cell production and activation during tissue repair after injury, and appear to drive proliferation in a variety of type of tumors, including those arising in the brain, foregut, lung, breast, pancreas, stomach, and prostate. Early evidence from Drosophila, and later work in vertebrates established the cAMP/protein kinase A (PKA) pathway as a major pathway which opposes HH signaling, doing so by phosphorylating intracellular signaling mediators and targeting them for degradation. Thus, it seems possible that ligands which activate G protein-coupled receptors (GPCR) may act in some cases to oppose or enhance HH signaling. We studied a possible interaction of pituitary adenylyl cyclase-activating peptide (PACAP) with sonic hedgehog (SHH) in the developing cerebellum, where both PACAP and SHH are know to act. PACAP and the PAC1-specific agonist, maxadilan, were found to completely block the proliferative action of SHH on developing cerebellar granule neurons. It remains to be determined if HH/GPCR antagonistic interactions play additional important roles in development, plasticity, tissue repair, cancer, and other processes.


Students classified as LD who petitioned for or fulfilled the college foreign language requirement-are they different? A replication study.
This replication study compared 86 petition students who received course substitutions for the college foreign language (FL) requirement with 40 nonpetition students who fulfilled the FL requirement by passing FL courses on cognitive and academic achievement measures and graduating grade point average. The results showed significant differences between the two groups, favoring the nonpetition group on one measure, the American College Testing (ACT) score, when IQ was used as a covariate; however, no significant group differences remained when ACT score was used as a covariate. More than half of the 126 petition and nonpetition students did not meet a minimum criterion for classification as learning disabled (LD), and more than half of both groups (54% and 63%, respectively) were not classified as LD before enrolling in college. Sixty percent of the petition students either had not taken an FL course in college or had achieved only grades of withdrawal before petitioning for substitution of the FL requirement. Implications addressed include petition students' persistence in fulfilling the FL requirement, students' use of instructional accommodations and services, criteria used to classify students as LD, use of the Modern Language Aptitude Test (MLAT), and why some students classified as LD pass FL courses and other students classified as LD do not.


EGFR T790M: revealing the secrets of a gatekeeper.
Non-small-cell lung cancers that harbor activating mutations in the EGFR gene represent an important molecularly defined subset of lung cancer. Despite dramatic initial responses with first- and second-generation EGFR-directed tyrosine-kinase inhibitors (TKIs) against these cancers, the development of a dominant and frequent resistance mechanism through a threonine-methionine amino acid substitution at position 790 (T790M) of EGFR has limited the long-term efficacy of these targeted therapies. This "gatekeeper" EGFR T790M alteration remains the only validated and relevant second-site resistance mutation for EGFR, allowing for focused research to understand and overcome EGFR T790M-mediated resistance. The current review focuses on EGFR T790M by discussing mechanisms of resistance mediated by EGFR T790M, reviewing development of novel third-generation EGFR TKIs targeting EGFR T790M, and highlighting current research on overcoming resistance to third-generation EGFR T790M TKIs.


Treatment of metastatic breast cancer: a large observational study on adherence to French prescribing guidelines and financial cost of the anti-HER2 antibody trastuzumab.
This observational study aimed at analyzing adherence to prescribing guidelines of anti-HER2 monoclonal antibody trastuzumab treatment for metastatic breast cancer. Efficacy and costs were also evaluated. The adherence to the trastuzumab treatment plan was analyzed according to both the French postlicensing guidelines published in 2001 and clinical guidelines from the regional cancer network in a cohort of 131 consecutive patients. The level of appropriateness to the molecular target was very high (92% of the patients showed a positive HER2 status, defined as HER2 3+ confirmed by immunohistochemistry or 2+ confirmed by fluorescent in situ hybridization). The treatment plan was made according to the French postlicensing guidelines in 41 patients (31.3%) and to the regional clinical guidelines for 109 patients (83.2%). The main reason for the difference was the type of molecules authorized for combination to trastuzumab. The median overall survival of the studied population was 18.6 months and the median progression-free survival rate was 7.7 months. Up to death or end of the study, the overall cost for the treatment of breast cancer with trastuzumab per patient and per year was 47,832 euro. This quite low adherence of clinicians to the French postlicensing guidelines is in contrast with the high level of adherence to the regional clinical guidelines. The reason is that the latter are less rigid about previously received treatments and enlarge the potential associated cytotoxics to vinorelbine. This supports the French National Cancer Institute decision to get expert clinicians involved together with the French agency for sanitary security of health products and the high health authority in a common elaboration of guidelines.


Identifying sources of stress and job satisfaction in the nursing environment.
As nursing has previously been identified as a stressful occupation (Tyler and Cushway 1992; 1995), sources of job stress and levels of job satisfaction were investigated in a study of occupational stress with 129 Victorian nurses. The study aimed to identify what the nurses perceived as the major causes of stress in the workplace using a standardized questionnaire, Gray-Toft and Anderson's Nursing Stress Scale (NSS), and by way of written reports. Level of job satisfaction was measured using the Nursing Stress Index (Harris Hingley and Cooper 1988). Results showed that the nurses rated their workload as highly stressful in terms of both frequency of its occurrence and its perceived effect upon themselves. As expected, higher levels of reported nursing stress were associated with lower levels of job satisfaction. Analyses of the written descriptions of a recent stressful work episode provided by 66 of the nurses included examples of relevant nursing stressors that were not covered by the NSS. Findings from the qualitative data are also discussed in terms of the implications for nursing practice arising from the impact of workload, and professional interpersonal conflicts.


Combretastatin A4 phosphate: a novel vascular disrupting agent.
Combretastatin A4 phosphate (CA4P) is the lead compound of a relatively new class of agents termed vascular disrupting agents that target existing tumor blood vessels. Rapid tumor blood flow shutdown has been demonstrated in preclinical models and patients by various techniques such as dynamic contrast-enhanced MRI, perfusion computed tomography and PET scans following CA4P infusion. CA4P typically induces rapid tumor necrosis in the center of the tumor and leaves a rim of viable cells in the periphery. In oncology, CA4P does not appear to be that active by itself, but may be more efficacious when combined with chemotherapy, antiangiogenic therapy and radiation therapy. Studies are currently underway, which combine CA4P with antiangiogenic agents. Side effects have included hypertension, tumor pain and occasional cardiovascular toxicity, without any significant myelosuppression or disabling systemic symptoms. The utility of CA4P for conditions other than cancer, which involves neovascularization such as macular degeneration, is also being explored.


Modelling Filler Dispersion in Elastomers: Relating Filler Morphology to Interface Free Energies via SAXS and TEM Simulation Studies.
The properties of rubber are strongly influenced by the distribution of filler within the polymer matrix. Here, we introduce a Monte Carlo-based morphology generator. The basic elements of our model are cubic cells, which, in the current version, can be either silica filler particles or rubber volume elements in adjustable proportion. The model allows the assignment of surface free energies to the particles according to whether a surface represents, for instance, 'naked' silica or silanised silica. The amount of silanisation is variable. We use a nearest-neighbour site-exchange Monte Carlo algorithm to generate filler morphologies, mimicking flocculation. Transmission electron micrographs (TEM) as well as small angle scattering (SAS) intensities can be calculated along the Monte Carlo trajectory. In this work, we demonstrate the application of our morphology generator in terms of selected examples. We illustrate its potential as a tool for screening studies, relating interface tensions between the components to filler network structure as characterised by TEM and SAS.


A comparative study of different presentation strategies for an HIV peptide immunogen.
Different strategies have been used to increase the immunogenicity of an antigenic HIV peptide as a vaccine candidate. The selected B-cell epitope comprises 15 amino acids (317-331) of the V3 region of HIV-1, JY1 isolate (subtype D), in tandem with a T-helper epitope corresponding to the 830-844 region of tetanus toxoid. Several presentations, including oligomerization, multiple antigenic peptide dendrimers, and conjugation to dextran beads or to other macromolecular carriers, have been synthesized and evaluated. Murine sera from the different presentations of the V3 epitope have been compared with regard to antibody titers and cross-reactivity with heterologous HIV subtypes. The dendrimer version of the peptide conjugated to HBsAg protein was a better immunogen than the dendrimer alone and showed a higher immunogenicity than other multimeric presentations or than the peptide alone conjugated to dextran. The dendrimer version, either alone or conjugated to HBSAg, enhanced cross-reactivity toward heterologous V3 sequences relative to monomeric peptide. In addition, fine epitope mapping of the entire JY1 sequence by sera from the different immunization groups was performed by the spot synthesis technique. Results showed that the amino acids involved in molecular recognition were LXQXXY or LXQXLY, with particularly strong recognition of the C-terminal region LGQALY. However, cross-reactivity toward the heterologous sequences did not completely correlate with recognition of particular amino acids in the primary sequences. These results can find application in the development of HIV vaccine candidates.


Population dynamics and their impact on adolescents in the ESCAP region.
"This study examines the impact on adolescents of the dramatic demographic, social and economic changes currently taking place in the ESCAP region. Among the aspects it considers are the growth of the adolescent population, their age at marriage and fertility, educational developments, labour force participation, and the effects of poverty, globalization and urbanization on this segment of the population. It concludes by drawing out the implications of the research for policy and programme purposes."


Innate immune natural killer cells and their role in HIV and SIV infection.
The findings that early events during HIV-1 and SIV infection of Asian rhesus macaques dictate the levels of viremia and rate of disease progression prior to the establishment of mature and effective adaptive immune responses strongly suggest an important role for innate immune mechanisms. In addition, the fact that the major target of HIV and SIV during this period of acute infection is the gastrointestinal tissue suggests that whatever role the innate immune system plays must either directly and/or indirectly focus on the GI tract. The object of this article is to provide a general overview of the innate immune system with a focus on natural killer (NK) cells and their role in the pathogenesis of lentivirus infection. The studies summarized include our current understanding of the phenotypic heterogeneity, the putative functions ascribed to the subsets, the maturation/differentiation of NK cells, the mechanisms by which their function is mediated and regulated, the studies of these NK-cell subsets, with a focus on killer cell immunoglobulin-like receptors (KIRs) in nonhuman primates and humans, and finally, how HIV and SIV infection affects these NK cells in vivo. Clearly much has yet to be learnt on how the innate immune system influences the interaction between lentiviruses and the host within the GI tract, knowledge of which is reasoned to be critical for the formulation of effective vaccines against HIV-1.


Does protein supplementation prevent muscle disuse atrophy and loss of strength?
Recently there has been much interest in the use of dietary amino acids supplements to decrease the losses in muscle mass and strength observed after space flight or during aging using bed rest analogs. This interest persists even if the results have been mixed. Of the six published amino acid supplementation studies, three showed benefit, three did not. A recent study re-evaluating protein requirements in humans suggests that the official RDA is 41% underestimated. Interestingly, the three studies that showed benefits fed their test subjects a baseline protein level around the old RDA for protein. The three that did not show benefit gave the subjects a baseline protein intake higher than the new RDA. We suggest that the positive effects observed on protein metabolism might just reflect the benefits of adequate protein intake achieved during bed rest rather than a protective effect against bed-rest induced disuse. In conclusion, the efficiency of amino acid countermeasures for preventing the loss in protein mass during space flight or bed rest needs to be seriously questioned. These results extend to clinical situations such as serious illness and progress of aging in which physical inactivity is a significant component of the loss in muscle function.


[Estrogens and the psyche].
Animal experiments have revealed much about location, mode and mechanism of action of oestrogens on the brain. It appears very likely from these experiments that oestrogens affect psychic functions. However, data proving such actions in the human are fragmentary and incomplete. It is generally assumed that physiological concentrations of oestrogens influence sexual and non-sexual behaviour, as well as mental performance in man, but the requisite scientific data are still insufficient in many cases to allow definite conclusions to be reached. Similarly, statements that moderately increased concentrations of oestrogens affect the psyche continue to be a matter of debate. In contrast it is established that both excess and deficiency of oestrogens can influence psychic functions in the human. This has been clearly demonstrated in extensive studies, particularly with regard to the psychic changes in the peri- and postmenopause, whereas little can be said about a cause-effect relationship between oestrogen deficiency and declining mental function with advancing age. The therapeutic value of oestrogen replacement in psychic disturbances associated with oestrogen deficiency states such as hypogonadism, after castration and in the climacteric is well documented by many studies. All other assumed psychic indications in the process of ageing are much less clearly defined and at present of questionable medical importance.


Probing intermittency and reversibility in a dense granular suspension under shear using multiply scattered ultrasound.
We study the rheology of a dense granular suspension under shear strain with the simultaneous detection of multiply scattered ultrasound through the shear band. At a low shear rate, the dissipation is rate-independent and determined by the frictional contacts between grains. Under quasistatic shear, the stress-strain curve contains elastic loading parts interrupted by stress drops. Such an intermittency is concomitant with some large decorrelation events as measured by the ultrasound probe, sensitive to the position of the grains. Under cyclic shear, the correlations between the scattered ultrasonic waves show that at low shear strain, the grains exhibit reversible motion. Beyond this linear regime, some irreversible motion of the grains is detected. Moreover, the correlation between successive ultrasound signals suggests that some specific rearrangements, which add to the homogeneous flow, take place near the maximum strain.


Scutellaria barbata D. Don inhibits colorectal cancer growth via suppression of Wnt/β-catenin signaling pathway.
To investigate the effect of the ethanol extract of Scutellaria barbata D. Don (EESB) on colorectal cancer (CRC) growth and Wnt/β-catenin signaling pathway in vivo and in vitro. In vivo experiment, CRC xenograft mouse model was constructed with injection of HT-29 cells. Following xenograft implantation, twenty mice were randomly divided into EESB-treated group (n=10) and control group (n=10) by a random number table, and were given with intra-gastric administration of 2 g/kg EESB or saline, 5 days a week for 16 days, respectively. At the end of experiment, tumors were removed and weighed by electronic scales. The proliferation biomarker Ki-67 of tumor was evaluated by immunohistochemistry (IHC) assay. In vitro study, HT-29 cells were treated with 0, 0.5, 1.5, 2.5 mg/mL EESB for 24 h. At the end of the treatment, the viability and survival of HT-29 cells were determined by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and colony formation assay, respectively. The mRNA expression of c-Myc, Survivin and adenomatous polyposis coli (APC) was examined by reverse transcription-polymerase chain reaction (RT-PCR) both in tumor tissues of CRC xenograft mice and HT-29 cells. Protein expression of c-Myc, Survivin, APC, and β-catenin as well as β-catenin phosphorylation level were evaluated by IHC assay or Western blotting. EESB significantly reduced tumor weight in CRC xenografts mice, compared with the control group (P<0.05). IHC assay showed that EESB significantly inhibited protein expression of Ki-67 in tumor tissues (P<0.05). MTT assay showed that EESB significantly reduced HT-29 cell viability in a dose-dependent manner (P<0.05). Colony formation assay showed that EESB dose-dependently decreased the survival of HT-29 cells (P<0.05). In addition, RT-PCR assay showed that EESB decreased the mRNA expression of c-Myc and Survivin and increased APC expression, both in tumor tissues of CRC xenograft mice and HT-29 cells (P<0.05). IHC assay or Western blotting showed that EESB decreased protein expression of β-catenin, c-Myc and Survivin, as well as increased APC expression and β-catenin phosphorylation in tumor tissues or HT-29 cells (P<0.05). EESB significantly reduced tumor growth in CRC xenografts mice, and inhibited the viability and survival of HT-29 cells. EESB could suppress the activation of the Wnt/β-catenin pathway, which might be one of the mechanisms whereby Scutellaria barbata D. Don exerts its anticancer activity.


Genomic Diversity of Burkholderia pseudomallei in Ceara, Brazil.
Burkholderia pseudomallei is a Gram-negative bacterium that causes the sapronotic disease melioidosis. An outbreak in 2003 in the state of Ceara, Brazil, resulted in subsequent surveillance and environmental sampling which led to the recognition of B. pseudomallei as an endemic pathogen in that area. From 2003 to 2015, 24 clinical and 12 environmental isolates were collected across Ceara along with one from the state of Alagoas. Using next-generation sequencing, multilocus sequence typing, and single nucleotide polymorphism analysis, we characterized the genomic diversity of this collection to better understand the population structure of B. pseudomallei associated with Ceara. We found that the isolates in this collection form a distinct subclade compared to other examples from the Western Hemisphere. Substantial genetic diversity among the clinical and environmental isolates was observed, with 14 sequence types (STs) identified among the 37 isolates. Of the 31,594 core single-nucleotide polymorphisms (SNPs) identified, a high proportion (59%) were due to recombination. Because recombination events do not follow a molecular clock, the observation of high occurrence underscores the importance of identifying and removing recombination SNPs prior to evolutionary reconstructions and inferences in public health responses to B. pseudomallei outbreaks. Our results suggest long-term B. pseudomallei prevalence in this recently recognized region of melioidosis endemicity.IMPORTANCEB. pseudomallei causes significant morbidity and mortality, but its geographic prevalence and genetic diversity are not well characterized, especially in the Western Hemisphere. A better understanding of the genetic relationships among clinical and environmental isolates will improve knowledge of the population structure of this bacterium as well as the ability to conduct epidemiological investigations of cases of melioidosis.


Semireannealing, single-stranded conformational polymorphism: a novel and effective tool for the diagnosis of T-cell clonality.
Single-stranded conformational polymorphism (SSCP) is often used for the diagnosis of T-cell clonality in lymphoproliferative disorders. We introduce a semireannealing SSCP (SR-SSCP) protocol that is rapid, reproducible, and effective. By denaturing and reannealing the polymerase chain reaction (PCR) product before high-resolution polyacrylamide gel electrophoresis, it is possible to generate a diagnostic fingerprint for each case with clonal T-cell receptor-gamma (TCR-gamma) gene rearrangement detected after PCR with TCR-gamma specific consensus primers. Discrete and distinct denatured single-stranded DNA band profiles characterize the rearranged TCR-gamma clones. In the same gel, the clone size may be estimated in the reannealed double-stranded PCR DNA and can be assessed down to the 2% clonal T-cell population level. Eighty-four cases, including 37 T-cell neoplasms, 29 B-cell neoplasms, and 18 reactive lymph node samples were analyzed by SR-SSCP. Clonal TCR-gamma rearrangement was diagnosed in 32 out of 37 T-cell neoplasms but in none of the B-cell tumors or reactive lymph node samples corresponding to sensitivity and specificity of 86.5% and 100%, respectively. We compare the results of SR-SSCP to those obtained by capillary electrophoresis and direct sequence analysis with 100% correlation. This novel method is applicable to any system for identification and quantitation of microheterogeneity in PCR products.


Two novel silicon phases with direct band gaps.
Due to its abundance, silicon is the preferred solar-cell material despite the fact that many silicon allotropes have indirect band gaps. Elemental silicon has a large impact on the economy of the modern world and is of fundamental importance in the technological field, particularly in the solar cell industry. Looking for direct band gap silicon is still an important field in material science. Based on density function theory with the ultrasoft pseudopotential scheme in the frame of the local density approximation and the generalized gradient approximation, we have systematically studied the structural stability, absorption spectra, electronic, optical and mechanical properties and minimum thermal conductivity of two novel silicon phases, Cm-32 silicon and P21/m silicon. These are both thermally, dynamically and mechanically stable. The absorption spectra of Cm-32 silicon and P21/m silicon exhibit significant overlap with the solar spectrum and thus, excellent photovoltaic efficiency with great improvements over Fd3[combining macron]m Si. These two novel Si structures with direct band gaps could be applied in single p-n junction thin-film solar cells or tandem photovoltaic devices.


Cardiac cell sheet transplantation improves damaged heart function via superior cell survival in comparison with dissociated cell injection.
Regenerative therapies have currently emerged as one of the most promising treatments for repair of the damaged heart. Recently, numerous researchers reported that isolated cell injection treatments can improve heart function in myocardial infarction models. However, significant cell loss due to primary hypoxia or cell wash-out and difficulty to control the location of the grafted cells remains problem. As an attempt to overcome these limitations, we have proposed cell sheet-based tissue engineering, which involves stacking confluently cultured cells (two-dimensional), cell sheets, to construct three-dimensional cell-dense tissues. Cell sheet transplantation has been able to recover damaged heart function. However, no detailed analysis for transplanted cell survival has been previously performed. The present study compared the survival of cardiac cell sheet transplantation to direct cell injection in a rat myocardial infarction model. Luciferase-expressing neonatal rat cardiac cells were harvested as cell sheets from temperature-responsive culture dishes. The transplantation of cell sheets was compared to the direct injection of isolated cells dissociated with trypsin-ethylenediaminetetraacetic acid. These grafts were transplanted to infarcted rat hearts and cardiac function was assessed by echocardiography at 2 and 4 weeks after transplantation. In vivo bioluminescence and histological analyses were performed to examine cell survival. Cell sheet transplantation consistently yielded greater cell survival than cell injection. Immunohistochemistry revealed that cardiac cell sheets existed over the infarcted area as an intact layer. In contrast, the injected cells were scattered with relatively few cardiomyocytes in the infarcted areas. Four weeks after transplantation, cardiac function was also significantly improved in the cell sheet transplantation group compared with the cell injection. Twenty-four hours after cell grafting, significantly greater numbers of mature capillaries were also observed in the cardiac cell sheet transplantation. Additionally, the numbers of apoptotic cells with deterioration of integrin-mediated attachment were significantly lower after cardiac cell sheet transplantation. In accordance with increased cell survival, cardiac function was significantly improved after cardiac cell sheet transplantation in comparison to cell injection. Cell sheet transplantation can repair damaged hearts through improved cell survival and should become a promising therapy in cardiovascular regenerative medicine.