beta-Adducin polymorphisms, blood pressure, and sodium excretion in three European populations.
The associations of the beta-adducin C1797T polymorphism with blood pressure (BP) and various indexes of sodium homeostasis were investigated in 388 men and 456 women, aged 18 to 60 years, recruited from three European populations (Cracow, Poland, n = 300; Novosibirsk, Russian Federation, n = 274; Mirano, Italy; n = 270). Phenotypes included 24-h ambulatory BP and urinary excretion of electrolytes and aldosterone. Subjects were genotyped for the beta-adducin polymorphism. Both a population-based association study and a family-based analysis were performed. Urinary sodium excretion was higher in Cracow than in Mirano (241 v 185 mmol/24 h, P <.05) and intermediate in Novosibirsk (206 mmol/24 h). The beta-adducin T allele (15.2% v 9.1%, P <.0001) was more prevalent in Mirano than in the two Slavic centers. In both population-based and family-based association analyses, there was significant heterogeneity between Slavic and Italian subjects in the phenotype-genotype relationships with beta-adducin. In the Slavic centers, 24-h systolic BP was higher in T allele carriers than in CC homozygotes (122.3 v 119.7 mm Hg, P =.03), whereas this was not the case in Mirano (121.8 v 122.9 mm Hg, P =.42). In Slavic (212.6 v 233.1 mmol/24 h) as well as in Italian (166.1 v 191.5 mmol/24 h) participants, 24-h sodium excretion was lower (P =.01) in T allele carriers than in CC homozygotes. These results were confirmed in the family-based analysis of offspring using a quantitative transmission disequilibrium test. In conclusion, the frequency of the beta-adducin T allele and salt intake differ across European populations. Thus, both variation in genetic background and salt intake may explain the observed heterogeneity in the phenotype-genotype relationships. Genetic determinants of complex quantitative traits such as BP can only be investigated within their epidemiologic context.


Dataset of "true mangroves" plant species traits.
Plant traits have been used extensively in ecology. They can be used as proxies for resource-acquisition strategies and facilitate the understanding of community structure and ecosystem functioning. However, many reviews and comparative analysis of plant traits do not include mangroves plants, possibly due to the lack of quantitative information available in a centralised form. Here a dataset is presented with 2364 records of traits of "true mangroves" species, gathered from 88 references (published articles, books, theses and dissertations). The dataset contains information on 107 quantitative traits and 18 qualitative traits for 55 species of "true mangroves" (sensu Tomlinson 2016). Most traits refer to components of living trees (mainly leaves), but litter traits were also included.


A growth arrest-specific (gas) gene codes for a membrane protein.
A set of growth arrest-specific (gas) genes whose expression is negatively regulated by serum has recently been identified. We report on the detailed analysis of one of these genes (gas3). The kinetics of regulation by the presence and absence of serum were investigated, and it was found that this gene is regulated at the post-transcriptional level. The encoded protein deduced from the nucleotide sequence showed some similarity to a mitochondrial oxyreductase, and in vitro translation established that the protein product is a transmembrane glycoprotein.


The clinicopathological significance of Bax and Bcl-2 protein expression with tumor infiltrating lymphocytes in ovarian carcinoma.
The aim of the study was to establish the prognostic and predictive value of Bax and Bcl-2 proteins in conjunction with the host immune response in primary epithelial ovarian carcinoma.83 patients were evaluated. Immunohistochemical staining was performed using anti-Bcl-2 (Dako; clone 124) and anti-Bax (Springbio; E17994) monoclonal antibodies. Additionally, the number of lymphocytes within tumor stroma lymphocyte nests were counted. Bcl-2 protein expression was lower in advanced stage than early stage (p= 0.005). High (H) Bax expression was associated with longer overall survival (OS) than lower (L) Bax expression (p=0.03). The OS of the (L) Bax/(L) Bcl-2 group was shorter than (H) Bax/(L) Bcl-2 group in advanced stage (p=0.05). The platinum-sensitive group had a statistically significant tendency for high Bax expression (p=0.04). Furthermore, the intensity of the lymphocyte infiltration was associated with tumor differentiation (p= 0.003). Our data suggests that (H) Bax protein expression prolongs survival, predicts platinum sensitivity and can be used after confirmation of this hypothesis in further prospective studies. The combined evaluation of Bax and Bcl-2 protein expression may provide additional significant prognostic information. The quantity of lymphocyte infiltration could be important for prognostic outcome.


Direct Nucleophilic Substitution Reaction of Cage B-H Bonds by Grignard Reagents: A Route to Regioselective B4-Alkylation of o-Carboranes.
Direct nucleophilic substitution reaction of cage B-H bonds of o-carboranes by Grignard reagents in the absence of any transition metals has been achieved for the first time, and leads to the regioselective synthesis of a series of 4-alkyl-1,2-diaryl-o-carboranes in very high yields. The presence of two electron-withdrawing aryl groups on the cage carbon atoms is crucial to realizing the reaction. The regioselectivity is controlled by both electronic and steric factors. This work represents a new strategy for the development of methods for carborane functionalization.


Dye-Anchored MnO Nanoparticles Targeting Tumor and Inducing Enhanced Phototherapy Effect via Mitochondria-Mediated Pathway.
Phototherapy is a promising treatment method for cancer therapy. However, the various factors have greatly restricted phototherapy development, including the poor accumulation of photosensitizer in tumor, hypoxia in solid tumor tissue and systemic phototoxicity. Herein, a mitochondrial-targeted multifunctional dye-anchored manganese oxide nanoparticle (IR808@MnO NP) is developed for enhancing phototherapy of cancer. In this nanoplatform, IR808 as a small molecule dye acts as a tumor targeting ligand to make IR808@MnO NPs with capacity to actively target tumor cells and relocate finally in the mitochondria. Meanwhile, continuous production of oxygen (O2 ) and regulation of pH induced by the high reactivity and specificity of MnO NPs toward mitochondrial endogenous hydrogen peroxide (H2 O2 ) could effectively modulate tumor hypoxia and lessen the tumor subacid environment. Large amounts of reactive oxide species (ROS) are generated during the reaction process between H2 O2 and MnO NPs. Furthermore, under laser irradiation, IR808 in IR808@MnO NPs turns O2 into a highly toxic singlet oxygen (1 O2 ) and generates hyperthermia. The results indicate that IR808@MnO NPs have the high efficiency of specific targeting of tumors, relieving tumor subacid environment, improving the tumor hypoxia environment, and generating large amounts of ROS to kill tumor cells. It is expected to have a wide application in treating cancer.


Patterns of using complementary and alternative medicine by stroke patients at two university hospitals in Korea.
This study measured the prevalence of complementary and alternative medicine (CAM) use among Korean stroke patients. Questionnaire-based 20-min interviews were conducted at the hospitals by a trained nurse after an outpatient visit. It included questions on demographic information, clinical information and the utilization of CAM. Of 304 stroke-patient respondents, 164 (54%) had used CAM, of which 66% had started taking CAM products following suggestions from family members and other relatives. Of the 57% of users who felt that CAM was effective, 84% considered that it improved the symptoms of stroke and 16% felt it was effective in achieving psychological relaxation. Of the eight CAM categories used by respondents, 92% used traditional Oriental medical treatments, 36% used plant- and animal-derived over-the-counter health care products, 24% used minerals and vitamins, and 11% used manual therapies. The majority of stroke patients (68%) were trying a new type of CAM, and half of the respondents (45%) relied on the knowledge of their general practitioner about CAMs when deciding whether to use them. Most of the stroke patients in this study used CAM, and a half of them reported beneficial effects. Despite the presence of adverse side effects, they tended to be used without discussion with chief physicians, and hence physicians should be actively involved in the usage of CAM.


Separation and characterization of maternal cardiac and vascular sounds in the third trimester of pregnancy.
To characterize the vascular sounds of the uteroplacental blood flow obtained by microphones. The present retrospective study took place in an anechoic chamber facility at Aalborg University, Aalborg, Denmark, in 2012, and included pregnant participants aged 18-40 years with a singleton pregnancy at 32-36 weeks and a parity of 0-2. Abdominal Doppler ultrasonography was performed bilaterally on the uterine arteries. Subsequently, in the same positions, sound recordings were performed with microphones. The derived raw sound signal was separated into two frequency ranges, and characterized accordingly. The mean pregnancy length among 25 participants was 33.6 ± 2.0 weeks. The pulsatility index of the uterine artery was 0.67 ± 0.24. All 50 recordings displayed the first and second maternal heart sounds (frequency 25-100 Hz), and in 17 of 50 recordings, maternal vascular murmurs (frequency 200-800 Hz) were present. The average pulse wave velocity between the maternal aortic valve and the uterine artery was estimated to be 6.6 ± 1.5 m/s. Maternal vascular murmurs in the frequency range of 200-800 Hz were identified as a possible marker of abnormal uteroplacental blood flow, and provide a means to measure the arterial pulse wave velocity.


[Effect of thromboxane A2 synthetase inhibitor (OKY-046) on leukotriene C4-induced airway hyperresponsiveness in guinea pigs].
In this study, we investigated the effects of peroral (p.o.) administration of a thromboxane A2 (TXA2) synthetase inhibitor, OKY-046, on the airway hyperresponsiveness (AHR) in guinea pigs induced by intravenous administration of leukotriene C4 (LTC4). A 3 micrograms/kg/hr LTC4 infusion induced airway wall thickening (AWT) and AHR to 1.8 and 3.6 micrograms/kg histamine bolus shot. OKY-046 100 mg/kg p.o. partially inhibited the AHR induced by LTC4 without inhibition of AWT. Previously, we have reported that LTC4-induced AHR was partially inhibited, to the same exert as by OKY-046, by TXA2 receptor antagonists, ONO-NT-126 and ONO-8809. These data suggest that intravenous administration of LTC4 generates TXA2, and TXA2 augments LTC4-induced AHR partially in guinea pigs.


Associations between subclinical hypocalcemia and postparturient diseases in dairy cows.
Dairy cows suffer blood Ca losses as lactation begins and might be affected by hypocalcemia in its clinical (total serum Ca concentration <1.50 mM) or subclinical form (total serum Ca concentration ≤2.14 mM). Several studies have suggested that hypocalcemia is associated with different health problems of the cow but results from different studies are not consistent. The objective of this study was to assess potential associations between subclinical hypocalcemia (SCHC) and displaced abomasum, intramammary infections, metritis, retained placenta, and ketosis. Also, the associations between SCHC and milk yield and reproductive function were evaluated. After discarding cows (32) with clinical hypocalcemia, a total of 764 cows from 6 different commercial farms were enrolled in this study. Blood samples were collected at 24 to 48 h postcalving and analyzed for total Ca concentration. Odds ratios of the different afflictions potentially associated with SCHC were calculated. Seventy-eight percent of the analyzed cows incurred SCHC. The occurrence of displaced abomasum, ketosis, retained placenta, and metritis was 3.7, 5.5, 3.4, and 4.3 times more likely, respectively, in cows that had SCHC than in cows with normocalcemia. Furthermore, the risk of incurring retained placenta or metritis increased in multiparous cows as serum Ca concentrations decreased compared with that in primiparous cows. Normocalcemic cows, independent of parity, were more likely to show their first estrus sooner after calving than SCHC cows, but no correlation was found between SCHC and other reproductive parameters. Different serum Ca concentration cutoffs were identified for several postpartum afflictions (≤1.93, ≤2.05, ≤2.05, and ≤2.10 mM for ketosis, retained placenta, metritis, and displaced abomasum, respectively). In conclusion, SCHC, defined as serum Ca ≤2.14 mM, is a frequent illness affecting the majority of the dairy cows with important repercussions on health. However, if SCHC were to be used to predict postpartum disease, different serum Ca cutoff points are likely to be needed because best predictive cutoff values varied among postpartum ketosis, displaced abomasum, retained placenta, and metritis.


Health care-associated hepatitis C virus infection.
Hepatitis C virus (HCV) is a blood-borne pathogen that has a worldwide distribution and infects millions of people. Care-associated HCV infections represented a huge part of hepatitis C burden in the past via contaminated blood and unsafe injections and continue to be a serious problem of public health. The present review proposes a panorama of health care-associated HCV infections via the three mode of contamination that have been identified: (1) infected patient to non-infected patient; (2) infected patient to non-infected health care worker (HCW); and (3) infected HCW to non infected patient. For each condition, the circumstances of contamination are described together with the means to prevent them. As a whole, the more important risk is represented by unsafe practices regarding injections, notably with the improper use of multidose vials used for multiple patients. The questions of occupational exposures and infected HCWs are also discussed. In terms of prevention and surveillance, the main arm for combating care-associated HCV infections is the implementation of standard precautions in all the fields of cares, with training programs and audits to verify their good application. HCWs must be sensitized to the risk of blood-borne pathogens, notably by the use of safety devices for injections and good hygiene practices in the operating theatre and in all the invasive procedures. The providers performing exposed-prone procedures must monitor their HCV serology regularly in order to detect early any primary infection and to treat it without delay. With the need to stay vigilant because HCV infection is often a hidden risk, it can be hoped that the number of people infected by HCV via health care will decrease very significantly in the next years.


A non-small cell lung cancer (NSCLC) patient harboring a rare epidermal growth factor receptor (EGFR) L858R/V843I mutation complex benefited from osimertinib: a case report.
Tyrosine kinase inhibitors (TKIs) have greatly improved the survival of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR)-TKI sensitive mutations such as L858R and exon 19 deletions. The third-generation EGFR-TKI osimertinib, an irreversible TKI, is approved as a therapy for advanced NSCLC with EGFR sensitive mutations. Recently, osimertinib showed antitumor activity against NSCLC in patients harboring an uncommon mutation such as an exon 20 insertion. Herein, we present a patient diagnosed with stage IV NSCLC with an EGFR L858R/V843I mutation complex who benefited remarkably from osimertinib therapy. The patient was a 41-year-old Chinese female who complained of backache in October 2018. Computed tomography (CT) and magnetic resonance imaging (MRI) scans showed a mass in the right lung and brain metastasis. A whole-body bone scan revealed bone metastases. Targeted next-generation sequencing (NGS) of hydrothorax was performed and the coexistence of somatic L858RI and V843I mutations in EGFR exon 21 was discovered on November 13, 2018. Osimertinib therapy (80 mg daily) was administered for 12 months which resulted in an initial partial response (PR). At that point, the right lower lung lesion enlarged, indicating disease progression. Thus, the patient began combination therapy with osimertinib (80 mg daily) and bevacizumab (500 mg daily), leading to disease stabilisation until June 2020. Of note, during treatment, the patient achieved sustained control of metastatic brain and bone lesions. To the best of our knowledge, we report here the first known case of an NSCLC patient with a somatic EGFR L858R/V843I mutation complex who responded well to osimertinib. Our findings provide theoretical guidance and expand the list of potential beneficiaries of EGFR-TKI therapy.


The SIEP-DIRECT'S Project on the discrepancy between routine practice and evidence. An outline of main findings and practical implications for the future of community based mental health services.
To highlight the major discrepancies that emerged between evidence and routine practice in the framework of the SIEP-DIRECT'S Project (DIscrepancy between Routine practice and Evidence in psychiatric Community Treatments on Schizophrenia). The Project was conducted in 19 Italian mental health services (MHS), with the aims of: (a) evaluating the appropriateness of the NICE Guidelines for Schizophrenia in the Italian context, (b) developing and testing a set of 103 indicators that operationalised preferred clinical practice requirements according to the NICE Guidelines, and (c) evaluating their actual application in Italian MHSs. The indicators investigated five different areas: common elements in all phases of schizophrenia; first episode treatment; crisis treatment; promoting recovery; the aggressive behaviour management. The NICE recommendations examined were judged in most instances to be appropriate to the Italian MHS context, and the indicators fairly easy to use. The more severe and frequently encountered evidence-practice discrepancies were: lack of written material, guidelines, and information to be systematically provided to users; lack of intervention monitoring and evaluation; difficulty in implementing specific and structured forms of intervention; difficulty in considering patients' family members as figures requiring targeted support themselves and who should also be regularly involved in the patient care process. The key actions to be undertaken to favour implementation of evidence-based routine practices are: focussing on mental illness onset and family support/involvement in care; planning training activities aimed at achieving specific treatment goals; encouraging MHS participation in evaluation activities; identifying thresholds for guideline application and promoting specific guideline implementation actions; and activating decision making and resource allocation processes that rely more strictly on evidence and epidemiological assessment. These considerations are of value for rethinking the model of community psychiatry in Italy as well as in other countries.


Microheterogeneity of brain dopamine in the experimental acute cerebral ischaemia.
In order to reveal the correlation of energy failure and neurotransmitter metabolism in the acute stage of incomplete cerebral ischaemia, the change of NADH (reduced form of nicotinamide adenine dinucleotide) and brain dopamine was studied histochemically using the same specimen on the unilateral carotid ligation of mongolian gerbils. The severity of clinical symptoms was well correlated with the extent and intensity of NADH fluorescence. Dopamine in the caudate nucleus on the ligated side decreased heterogeneously shortly after the cerebral ischaemia. Preservation of dopamine was noted around the small vessels with thick walls. Thus, heterogeneity of dopamine decrease appears to be closely related to the structure of microvasculature. It was seen in areas of heterogeneously increased NADH, but also in areas of its homogeneous increase within 5 to 60 min after carotid ligation. This microheterogeneity of brain dopamine may be due to the difference of perfusion pressure at the microcirculation in the acute stage of incomplete cerebral ischaemia.


Measuring population health risks using inpatient diagnoses and outpatient pharmacy data.
To examine and evaluate models that use inpatient encounter data and outpatient pharmacy claims data to predict future health care expenditures. The study group was the privately insured under-65 population in the 1997 and 1998 MEDSTAT Market Scan (R) Research Database. Pharmacy and disease profiles, created from pharmacy claims and inpatient encounter data, respectively, were used separately and in combination to predict each individual's subsequent-year health care expenditures. The inpatient-diagnosis model predicts well for the low-hospitalization under-65 populations, explaining 8.4 percent of future individual total cost variation. The pharmacy-based and in patient-diagnosis models perform comparably overall, with pharmacy data better able to split off a group of truly low-cost people and inpatient diagnoses better able to find a small group with extremely high future costs. The model th at uses both kinds of data performed significantly better than either model alone, with an R2 value of 11.8 percent . Comprehensive pharmacy and inpatient diagnosis classification systems are each helpful for discriminating among people according to their expected costs. Properly organized and in combination these data are promising predictors of future costs.


Ontogenetic Differences in Dietary Fat Influence Microbiota Assembly in the Zebrafish Gut.
Gut microbiota influence the development and physiology of their animal hosts, and these effects are determined in part by the composition of these microbial communities. Gut microbiota composition can be affected by introduction of microbes from the environment, changes in the gut habitat during development, and acute dietary alterations. However, little is known about the relationship between gut and environmental microbiotas or about how host development and dietary differences during development impact the assembly of gut microbiota. We sought to explore these relationships using zebrafish, an ideal model because they are constantly immersed in a defined environment and can be fed the same diet for their entire lives. We conducted a cross-sectional study in zebrafish raised on a high-fat, control, or low-fat diet and used bacterial 16S rRNA gene sequencing to survey microbial communities in the gut and external environment at different developmental ages. Gut and environmental microbiota compositions rapidly diverged following the initiation of feeding and became increasingly different as zebrafish grew under conditions of a constant diet. Different dietary fat levels were associated with distinct gut microbiota compositions at different ages. In addition to alterations in individual bacterial taxa, we identified putative assemblages of bacterial lineages that covaried in abundance as a function of age, diet, and location. These results reveal dynamic relationships between dietary fat levels and the microbial communities residing in the intestine and the surrounding environment during ontogenesis. The ability of gut microbiota to influence host health is determined in part by their composition. However, little is known about the relationship between gut and environmental microbiotas or about how ontogenetic differences in dietary fat impact gut microbiota composition. We addressed these gaps in knowledge using zebrafish, an ideal model organism because their environment can be thoroughly sampled and they can be fed the same diet for their entire lives. We found that microbial communities in the gut changed as zebrafish aged under conditions of a constant diet and became increasingly different from microbial communities in their surrounding environment. Further, we observed that the amount of fat in the diet had distinct age-specific effects on gut community assembly. These results reveal the complex relationships between microbial communities residing in the intestine and those in the surrounding environment and show that these relationships are shaped by dietary fat throughout the life of animal hosts.


Endoscopic laser excisional biopsy for selected glottic carcinomas.
From January 1988 to December 1990, 44 previously untreated patients with squamous cell carcinomas (SCCs) of the true vocal cord (33 T1a, 11 Tis) underwent carbon dioxide laser excision. The mean follow-up was 28 months (range, 12 to 44 months). Endoscopic excisional biopsy was the primary treatment in 38 of the 44 patients, whereas postoperative radiotherapy was added in 6 cases in which the pathology report showed positive margins. Recurrent vocal cord SCC developed in 8 (18%) of the cases, with an average interval of 17.8 months. Re-treatment consisted of a second laser excision in 4 cases, radiotherapy in 1, hemilaryngectomy in 1, and total laryngectomy in 2. The definitive cure rate with endoscopic excisional biopsy for the patients originally treated with laser excision alone was 94.7% (36/38). Endoscopic laser treatment for selected glottic SCC proves to be an excellent alternative to radiotherapy or open neck surgery.


Ophthalmic antiviral chemotherapy: an overview.
Antiviral drug development has been slow due to many factors. One such factor is the difficulty to block the viral replication in the cell without adversely affecting the host cell metabolic activity. Most of the antiviral compounds are analogs of purines and pyramidines. Currently available antiviral drugs mainly inhibit viral nucleic acid synthesis, hence act only on actively replicating viruses. This article presents an overview of some of the commonly used antiviral agents in clinical ophthalmology.


The Saprophytic Lifestyle of Listeria monocytogenes and Entry Into the Food-Processing Environment.
Listeria monocytogenes is an environmentally adapted saprophyte that can change into a human and animal bacterial pathogen with zoonotic potential through several regulatory systems. In this review, the focus is on the occurrence of Listeria sensu stricto and sensu lato in different ecological niches, the detection methods, and their analytical limitations. It also highlights the occurrence of L. monocytogenes genotypes in the environment (soil, water, and wildlife), reflects on the molecular determinants of L. monocytogenes for the saprophytic lifestyle and the potential for antibiotic resistance. In particular, the strain-specific properties with which some genotypes circulate in wastewater, surface water, soil, wildlife, and agricultural environments are of particular interest for the continuously updating risk analysis.


Anti-osteoporosis therapy and fracture healing.
A number of medications are approved for treatment of osteoporosis. As mode of action usually is anti-catabolic/anti-resorptive or anabolic, it is of interest to know whether these drugs affect not only normal bone remodeling, but also fracture healing. The purpose of this paper is to give a short overview of the potential effect of various anti-osteoporotic medication on fracture healing. A narrative literature review was performed to describe the current knowledge. Anti-catabolic/anti-resorptive drugs: for bisphosphonates, the most common class of drugs in this group, experimental studies have shown a larger and stronger callus and delayed remodeling but no evidence of delayed healing. A human monoclonal antibody to RANKL is another anti-catabolic drug, with the only report to date showing enhanced healing in an animal model. Strontium ranelate is a drug where both anti-catabolic and a weak anabolic effect have been proposed, with experimental data ranging from no effect to significant increase in both callus volume and strength. Anabolic drugs: PTH has demonstrated accelerated healing of various experimental fractures and of distal radius and pelvic fractures in humans. While the exact mechanism is not fully understood, PTH results in increased recruitment and differentiation of chondrocytes and enhancement of endochondral ossification. A monoclonal antibody to block sclerostin is another potential anabolic pathway, where animal data have shown increase in bone mass and strength. The potential effect on fracture healing is yet to be studied. There are still large gaps in the understanding of the potential effect of anti-osteoporotic drugs on fracture healing, although based on present knowledge a recent or present fracture should not be considered as a contraindication to such treatment.


Electrodiagnostic studies in clinical trials for motor neuron disease.
Motor neuron disease (MND) is a group of neurodegenerative disorders characterized by death of upper motor neurons (UMN) and lower motor neurons (LMN). Clinical study of UMN loss is limited, but electrodiagnostic studies can be used readily to assess the functional state of LMN. Electrodiagnostic studies are regularly used in making the diagnosis of amyotrophic lateral sclerosis (ALS) and other forms of MND. They can also be used to follow disease progression and serve as end point measures in drug trials. In this role, electrodiagnostic studies can provide specific information not readily available from measurement of muscle strength or clinical functional scales. This article emphasizes the primary pathologic and secondary physiologic changes that take place after LMN loss and how they can be assessed by electrodiagnostic studies. It reviews the uses of routine electrodiagnostic studies for the diagnosis of MND but focuses on how special electrodiagnostic studies can be used as end point measures in drug trials.


RNA interference-mediated FANCF silencing sensitizes OVCAR3 ovarian cancer cells to adriamycin through increased adriamycin-induced apoptosis dependent on JNK activation.
In the present study, we downregulated FANCF expression by small interfering RNA (siRNA) in OVCAR ovarian cancer cells to address the effects of decreased FANCF expression on the function of the Fanconi anemia (FA)/breast cancer susceptibility gene (BRCA) pathway. Furthermore, we investigated whether this method increases the sensitivity of OVCAR3 cells to adriamycin (ADM) and the possible mechanism(s). We found that silencing of FANCF inactivated the FA/BRCA pathway by decreasing the monoubiquitination and focus formation of FANCD2 and reduced the function of the FA/BRCA pathway, resulting in the inhibition of cell proliferation, increased cell apoptosis and DNA damage in OVCAR3 cells. Moreover, we observed that silencing of FANCF enhanced the antiproliferative effect of ADM in OVCAR3 cells and increased ADM intracellular accumulation consequently sensitizing OVCAR3 cells to ADM. Furthermore, silencing of FANCF increased cell apoptosis of OVCAR3 cells which was caused by decreased mitochondrial membrane potential (MMP)-induced DNA damage, activated Jun N-terminal kinase (JNK), increased release of cytochrome c, increased expression of cleaved caspase-3 and poly(ADP-ribose) polymerase (PARP) dependent on JNK activation following treatment of ADM. Collectively, we confirm that silencing of FANCF sensitizes OVCAR3 ovarian cancer cells to ADM, suggesting that FANCF may serve as a potential target for therapeutic strategies in the treatment of ovarian cancer.


Dietary fiber: classification, chemical analyses, and food sources.
Dietary fiber's role in the prevention and treatment of constipation has long been known, but now fiber is touted as a cure for many of the ills in Western countries. Although some data exist to relate dietary fiber intake to certain diseases, lack of agreement on what dietary fiber is and how it should be measured make interpreting the data difficult. Further, not all dietary fiber is created equal. Water-soluble fibers, such as pectin and gums, have little effect on stool weight and hence are not appropriate treatment for patients with constipation. Water-insoluble fibers, such as cellulose and hemicellulose, are most effective in aiding laxation but may also limit absorption of minerals and possibly vitamins. Wheat bran is a good source of hemicellulose; vegetables supply cellulose to the diet. Most agencies are recommending a doubling or tripling of dietary fiber intake. Typical recommendations are set at 25 to 50 grams of dietary fiber daily. Different analytical methods for dietary fiber yield conflicting fiber values, and dietary fiber values do not exist for many foods, making fiber recommendations controversial and difficult to achieve. Fiber in the diet should ideally be increased by the consumption of unrefined breads and cereals and more fruits and vegetables. Vegetarians routinely consume 40 to 50 gm dietary fiber daily without ill effect. Fiber supplements may be appropriate for some patients, but the composition of the fiber should be known and be appropriate for the disease being treated. Before fiber supplements are marketed, clinical trials should be conducted to support the use of the supplements in the prevention and treatment of disease.(ABSTRACT TRUNCATED AT 250 WORDS)


THE PROBABILITY OF PEAK SHIFTS IN A FOUNDER POPULATION. II. AN ADDITIVE POLYGENIC TRAIT.
Stochastic shifts between two alternative stable equilibria in an additive polygenic system are modelled. The effect of selection on the character is represented by a double-peaked function relating individual fitness to phenotypic value. The mean of a large population will equilibrate near one of the two peaks, although with weak selection there may be a substantial displacement from the closest peak, due to the attraction exerted by the other peak. It is assumed that a small population is founded as a random sample from a large population at equilibrium under selection, and that genetic drift and selection interact to determine the evolution of the mean and variance of the polygenic character during the phase of exponential population growth that follows the foundation of the population. The effects on the frequencies of peak shifts of selectively induced linkage disequilibrium, randomly induced linkage disequilibrium, and random deviations from Hardy-Weinberg equilibrium are investigated by computer simulation. The results are compared with the probabilities of shifts calculated by an approximate analytic method. It is found that the approximations are reasonably accurate when the heights of the peaks in fitness are similar, but the approximations fail when one of the peaks is much higher than the other. The probability of a peak shift is shown to be a decreasing function of the strength of selection on the character. Although substantial changes in phenotypic mean can be induced by a founder event, the probability of a peak shift that induces a significant degree of reproductive isolation is low. The significance of these findings in relation to theories of speciation is discussed.


FLASH radiotherapy: A promising new method for radiotherapy.
Among the treatments for malignant tumors, radiotherapy is of great significance both as a main treatment and as an adjuvant treatment. Radiation therapy damages cancer cells with ionizing radiation, leading to their death. However, radiation-induced toxicity limits the dose delivered to the tumor, thereby constraining the control effect of radiotherapy on tumor growth. In addition, the delayed toxicity caused by radiotherapy significantly harms the physical and mental health of patients. FLASH-RT, an emerging class of radiotherapy, causes a phenomenon known as the 'FLASH effect', which delivers radiotherapy at an ultra-high dose rate with lower toxicity to normal tissue than conventional radiotherapy to achieve local tumor control. Although its mechanism remains to be fully elucidated, this modality constitutes a potential new approach to treating malignant tumors. In the present review, the current research progress of FLASH-RT and its various particular effects are described, including the status of research on FLASH-RT and its influencing factors. The hypothetic mechanism of action of FLASH-RT is also summarized, providing insight into future tumor treatments.


Mechanism of glutathione depletion during simulated ischemia-reperfusion of H9c2 cardiac myocytes.
It has been reported that myocardial glutathione content is decreased during ischemia-reperfusion, but the mechanism of glutathione depletion has remained unclear. The present study tested whether osmotic stress is involved in the glutathione depletion during ischemia. Six hours of hypoxic acidosis with either high CO(2) tension or low HCO(3)(-) concentration, which simulates the ischemic condition, resulted in a significant decrease of glutathione content and the glutathione depletion was prevented by hyperosmolarity. High-CO(2) acidosis alone without hypoxia induced a similar degree of glutathione depletion. Intracellular pH was lowered by high-CO(2) acidosis to 6.41 ± 0.03 in 15 min. Meanwhile, the cell size gradually increased and reached ∼110% in 10 min and the increased cell size was maintained for at least 30 min, which was also prevented by hyperosmolarity. Subsequent experiments observed the effects of simulated reperfusion on the glutathione content. Measured in 1 h after the hypoxic acidotic reperfusion, the glutathione content was further decreased compared to the level at the end of ischemia, which was not suppressed by increasing the osmolarity of reperfusion solution. The degree of glutathione depletion during hypoxic reperfusion with normal pH was similar to the hypoxic acidotic reperfusion group. On the other hand, normoxic reperfusion was not accompanied by further depletion of glutathione content. Based on these results, it was concluded that ischemia induces the glutathione depletion via osmotic stress, which results from intracellular acidification, and the glutathione content is further decreased during reperfusion through a mechanism other than oxygen toxicity.


Salicylates promote mitochondrial biogenesis by regulating the expression of PGC-1α in murine 3T3-L1 pre-adipocytes.
Mitochondrial dysfunction has been associated with insulin resistance and diabetes. Decreased mitochondrial density and mitochondrial copy numbers have been found in insulin-resistant individuals. Restoration of the number of mitochondria and normal mitochondrial function has become an important therapeutic target of diabetes. Salicylate, the main active ingredient in aspirin, has been in medicinal use since ancient times. Little information regarding the effects of salicylate on mitochondrial function has been reported. In this study, we assessed the effects of salicylate on the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) signaling pathway and mitochondrial biogenesis in pre-adipocytes. Our findings demonstrate that treatment with salicylate promoted the expression of PGC-1α and its downstream targets nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM). Importantly, salicylate treatment significantly increased the number of mDNA, citrate synthase activity, expression of respiratory chain complex I, and mitochondrial mass, which were suppressed by the specific AMPK inhibitor Compound C. Indeed, salicylate treatment induced the phosphorylation of AMPK, which was involved in the induction of PGC-1α, NRF1, and TFAM. Importantly, inhibition of PGC-1α expression using PGC-1α small RNA interference abolished the effects of salicylate on mitochondrial biogenesis. These results suggest that salicylate has a potential therapeutic capacity against mitochondrial dysfunction in diabetes.


The Vacuolar Molybdate Transporter OsMOT1;2 Controls Molybdenum Remobilization in Rice.
Molybdenum (Mo) is an essential micronutrient for almost all living organisms. The Mo uptake process in plants has been well investigated. However, the mechanisms controlling Mo translocation and remobilization among different plant tissues are largely unknown, especially the allocation of Mo to rice grains that are the major dietary source of Mo for humans. In this study, we characterized the functions of a molybdate transporter, OsMOT1;2, in the interorgan allocation of Mo in rice. Heterologous expression in yeast established the molybdate transport activity of OsMOT1;2. OsMOT1;2 was highly expressed in the blades of the flag leaf and the second leaf during the grain filling stage. Subcellular localization revealed that OsMOT1;2 localizes to the tonoplast. Knockout of OsMOT1;2 led to more Mo accumulation in roots and less Mo translocation to shoots at the seedling stage and to grains at the maturity stage. The remobilization of Mo from older leaves to young leaves under molybdate-depleted condition was also decreased in the osmot1;2 knockout mutant. In contrast, overexpression of OsMOT1;2 enhanced the translocation of Mo from roots to shoots at the seedling stage. The remobilization of Mo from upper leaves to grains was also enhanced in the overexpression lines during grain filling. Our results suggest that OsMOT1;2 may function as a vacuolar molybdate exporter facilitating the efflux of Mo from the vacuole into the cytoplasm, and thus, it plays an important role in the root-to-shoot translocation of Mo and the remobilization of Mo from leaves to grains.


Self-assembly of hybrid organic-inorganic polyoxomolybdates: solid-state structures and investigation of formation and core rearrangements in solution.
We report here a facile synthetic and analytical approach that allows us to identify and characterize functionalized polyoxomolybdate clusters that form upon the partial reduction of Mo(VI) salts in the presence of organoarsonate ligands. We demonstrated that electrospray ionization mass spectrometry, in combination with X-ray crystallography, provides an extremely powerful tool, allowing us to exploit slight perturbations of the ligand structures for the preparation of a series of unprecedented cluster compounds. Redox-active transition metals that adopt cubane or related structures are of particular interest because of their resemblance to active sites of enzymes. Our investigations underline the stability of the hybrid compounds in solution, an essential requirement for potential applications as catalysts. Supplemental analyses include measurements of the magnetic properties, NMR, IR, UV/vis, and bond-valence-sum analyses. Our results highlight the possibility of exploring real-time growth reactions of polyoxometales that emerge in solution and transform to produce hybrid organic-inorganic polyoxometalate clusters.


Obstetrical concerns of epidermolysis bullosa.
Epidermolysis bullosa is a group of autosomally inherited diseases involving skin breakdown of varying degrees and severity. Prenatal diagnosis and evaluation of these diseases is reviewed although pregnancy is not generally adversely affected by these diseases. Labor and delivery practices must be altered for the management of these patients. The obstetrical team must pay careful attention to adhesive dressings and anesthetic devices. Minor trauma may lead to severe lesions.


Quality of basic health care and social vulnerability: a spatial analysis.
To analyze the association between quality of basic health care and social vulnerability in municipalities of the Brazilian northeast. Ecological study with spatial analysis using univariate global and local Moran's indexes. Bivariate analyses were employed to examine the relationship between the quality of basic health care and the Social Vulnerability Index in the Northeast. The dependent variable corresponded to the final scores of certifications of teams of basic health care in the Northeast that had participated in the third cycle of the Brazilian Program for the Improvement of Access and Quality of Basic Health Care. The independent variable was the Social Vulnerability Index of the municipality. The bivariate analysis has pointed out the presence of areas of low vulnerability with high quality basic health care in the municipalities in the states of Piauí, Ceará, Rio Grande do Norte, Pernambuco, and Bahia. The state of Maranhão is emphasized for its low performance in basic health care in a large number of municipalities with high vulnerability. The study has revealed a spatial relation between the indicators of social vulnerability and quality of basic health care in the Northeast, suggesting that limitations in access to health resources and services may be related to social and health determinants.


Effects of transitory lingual nerve impairment on speech: an acoustic study of vowel sounds.
The purpose of the study was to evaluate the effects of the lingual nerve impairment on phonetic quality of speech by analyzing the main acoustic features of vowel sounds when the normal lingual nerve function was partly distorted by local anesthesia. The study group consisted of 7 men, whose right side lingual nerve was anesthetized with 0.8 mL of Ultracaine D-Suprarenin (Aventis Pharma Deutschland GmpH, Frankfurt am Main, Germany). The speech material analyzed consisted of 8 vowels produced in sentence context by speakers. Every utterance was repeated 10 times with and without local anesthesia. After recording, the speech samples were analyzed with a computerized speech laboratory. In addition, the vowels of 1 man with permanent nerve impairment were studied. The results show that the deprived function of the tongue after lingual nerve impairment had various effects on vowel quality for every subject. The main acoustic determinants of different vowels, the lowest vocal tract resonances, changed in frequency. In addition, the total duration of vowels changed and the vowels had different fundamental frequencies. However, these effects were extremely individual and variable. According to the results of acoustic analysis, the distortion of lingual nerve function has effects on vowel production. Some of these changes were so extensive that they also could be perceptually detectable. Lingual nerve impairment seems to have potential to change speech production.


Chromosome structure as revealed by a combined chemical and immunochemical procedure.
Human metaphase chromosomes were photooxidized in the presence of methylene blue, a process that destroys guanine residues in DNA. Indirect immunofluorescence showed that such chromosomes reacted with a cytosine-specific antibody revealing a consistent fluorescent banding pattern by which each chromosome could be identified. The observed fluorescent patterns were the reverse of those produced in formamide-denatured chromosomes treated with an antibody specific for adenine and of the patterns obtained with quinacrine and with Giemsa staining by the G-banding techniques. The patterns were identical to Giemsa R-banding patterns. The chromosome banding patterns, therefore, appeared to reflect DNA base composition, indicating the feasibility of a combined chemical-immunochemical investigation of the chemical organization of chromosomes.


Severity of Demyelinating and Axonal Neuropathy Mouse Models Is Modified by Genes Affecting Structure and Function of Peripheral Nodes.
Charcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous group of inherited polyneuropathies. Mutations in 80 genetic loci can cause forms of CMT, resulting in demyelination and axonal dysfunction. The clinical presentation, including sensory deficits, distal muscle weakness, and atrophy, can vary greatly in severity and progression. Here, we used mouse models of CMT to demonstrate genetic interactions that result in a more severe neuropathy phenotype. The cell adhesion molecule Nrcam and the Na+ channel Scn8a (NaV1.6) are important components of nodes. Homozygous Nrcam and heterozygous Scn8a mutations synergized with both an Sh3tc2 mutation, modeling recessive demyelinating Charcot-Marie-Tooth type 4C, and mutations in Gars, modeling dominant axonal Charcot-Marie-Tooth type 2D. We conclude that genetic variants perturbing the structure and function of nodes interact with mutations affecting the cable properties of axons by thinning myelin or reducing axon diameter. Therefore, genes integral to peripheral nodes are candidate modifiers of peripheral neuropathy.


Bioinformatics Analysis of Hub Genes Involved in Smoke-Induced Hemifacial Microsomia Pathogenesis.
Tobacco smoke is a recognized teratogen, which increases the risk for hemifacial microsomia (HFM) of the fetus during maternal pregnancy. The present study aimed to explore potential mechanisms and verify hub genes of HFM associated with smoke and tobacco smoke pollution (TSP) via bioinformatics methods. Hemifacial microsomia and smoke and TSP pathogenic genes were obtained. A protein-protein interactional (PPI) network was constructed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and molecular complex detection were performed by Metascape. Finally, we used the cytoHubba plug-in to screen the hub genes. A total of 43 HFM genes and 50 optimal smoke candidate genes were selected. Functional enrichment analysis largely focused on tissue morphogenesis and development. Two modules were identified from the PPI network, and 10 hub genes were screened out. The genes most relevant to smoke-induced HFM pathogenesis included TP53 , ESR1 , ESR2 , and HNRNPL. This study identified some significant hub genes, pathways, and modules of HFM related to smoke by bioinformatics analyses. Our results suggest that the TP53 , ESR1 , ESR2 , and HNRNPL gene subfamilies may have played a major role in HFM induced by smoke and TSP.


Case report: spinal epidural abscess from Klebsiella pneumoniae.
We report a rare case of cervical spinal epidural abscess due to Klebsiella pneumoniae. While the most likely pathogen is Staphylococcus aureus, 2.5% of CNS infections have been attributed to Klebsiella pneumoniae. The source of infection in this case is suspected to be from cervical vertebra osteomyelitis/discitis that expanded to epidural space. Prompt drainage of the abscess by decompression with debridement is the key of management that is shown to decrease morbidity and mortality in epidural abscess patients.


Effects of Gait Speed of Femoroacetabular Joint Forces.
Alterations in hip joint loading have been associated with diseases such as arthritis and osteoporosis. Understanding the relationship between gait speed and hip joint loading in healthy hips may illuminate changes in gait mechanics as walking speed deviates from preferred. The purpose of this study was to quantify hip joint loading during the gait cycle and identify differences with varying speed using musculoskeletal modeling. Ten, healthy, physically active individuals performed walking trials at their preferred speed, 10% faster, and 10% slower. Kinematic, kinetic, and electromyographic data were collected and used to estimate hip joint force via a musculoskeletal model. Vertical ground reaction forces, hip joint force planar components, and the resultant hip joint force were compared between speeds. There were significant increases in vertical ground reaction forces and hip joint forces as walking speed increased. Furthermore, the musculoskeletal modeling approach employed yielded hip joint forces that were comparable to previous simulation studies and in vivo measurements and was able to detect changes in hip loading due to small deviations in gait speed. Applying this approach to pathological and aging populations could identify specific areas within the gait cycle where force discrepancies may occur which could help focus management of care.


Pathways from interpersonal violence to sexually transmitted infections: a mixed-method study of diverse women.
This research sought to delineate the pathways that link experiences of abuse in women's lives to heightened risk for sexually transmitted infections (STIs), including HIV/AIDS. It was hypothesized that ethnically diverse abused women would not only be at greater risk for STI/HIV than their nonabused counterparts but would also experience unique, abuse-related risks. In order to bridge the findings of previous studies examining abuse-generated sexual risk, this study employed a mixed-method approach that elicited data from both life-history interviews of 28 abused women and structured interviews with 215 abused and nonabused women. In the first stage of analysis, multiple coders used a combination of inductive/open and deductive/precoded text analysis to delineate patterns of sexual risks in transcripts of abused women's life histories. Next, correspondence analysis, a tool that graphically illustrates the degree of similarity or difference between variables and participants, was performed on structured interview data in order to ascertain the relationship between specific risk factors and participants' levels of abuse/affection. Logistic regression of structured data tested for the effects of ethnicity. Both life-history and structured interview data revealed that a history of violence heightens STI/HIV risk in multiple interrelated ways, which include depression, substance abuse, exchange sex, first sex at an early age, high numbers of lifetime and current sexual partners, unfaithful partners, and inability to negotiate safe sex. As the severity/frequency of lifetime abuse increased, so too did sexual risk regardless of standard sociodemographic factors or ethnicity of participants. The domestic violence literature indicates an association between violence and STI/HIV risk. Findings from this mixed-method research provide a detailed account of the pathways that link the two.


The Prognostic Impact of NK/NKT Cell Density in Periampullary Adenocarcinoma Differs by Morphological Type and Adjuvant Treatment.
Natural killer (NK) cells and NK T cells (NKT) are vital parts of tumour immunosurveillance. However, their impact on prognosis and chemotherapy response in periampullary adenocarcinoma, including pancreatic cancer, has not yet been described. Immune cell-specific expression of CD56, CD3, CD68 and CD1a was analysed by immunohistochemistry on tissue microarrays with tumours from 175 consecutive cases of periampullary adenocarcinoma, 110 of pancreatobiliary type (PB-type) and 65 of intestinal type (I-type) morphology. Kaplan-Meier and Cox regression analysis were applied to determine the impact of CD56+ NK/NKT cells on 5-year overall survival (OS). High density of CD56+ NK/NKT cells correlated with low N-stage and lack of perineural, lymphatic vessel and peripancreatic fat invasion. High density of CD56+ NK/NKT cells was associated with prolonged OS in Kaplan-Meier analysis (p = 0.003), and in adjusted Cox regression analysis (HR = 0.49; 95% CI 0.29-0.86). The prognostic effect of high CD56+ NK/NKT cell infiltration was only evident in cases not receiving adjuvant chemotherapy in PB-type tumours (p for interaction = 0.014). This study demonstrates that abundant infiltration of CD56+ NK/NKT cells is associated with a prolonged survival in periampullary adenocarcinoma. However, the negative interaction with adjuvant treatment is noteworthy. NK cell enhancing strategies may prove to be successful in the management of these cancers.


Multifunctional and High Affinity Polymer Ligand that Provides Bio-Orthogonal Coating of Quantum Dots.
We detail the design of hydrophilic metal-coordinating ligands and their use for the effective coating of luminescent quantum dots (QDs). The ligand design exploits the specific, reagent-free nucleophilic addition reaction of amine-modified molecules toward maleic anhydride to introduce several lipoic acid metal anchors, hydrophilic zwitterion moieties, and specific reactive groups along a poly(isobutylene-alt-maleic anhydride) (PIMA) chain. Tunable reactive groups tested in this study include azide, biotin, carboxyl, and amine. Cap exchange with these multilipoic acid ligands via a photochemical ligation strategy yields homogeneous QD dispersions that are colloidally stable over several biologically relevant conditions and for extended periods of time. The zwitterionic coating yields compact nanoparticle size and imparts nonsticky surface properties onto the QDs, preventing protein absorption. The introduction of a controllable number of reactive groups allows conjugation of the QDs to biomolecules via bio-orthogonal coupling chemistries including (1) attachment of the neurotransmitter dopamine to QDs via amine-isothiocyanate reaction to produce a platform capable of probing interactions with cysteine in proteins, based on charge transfer interactions; (2) self-assembly of biotinylated QDs with streptavidin-dye; and (3) ligation of azide-functionalized QDs to cyclooctyne-modified transferrin via copper-free click chemistry, used for intracellular delivery. This ligand design strategy can be used to prepare an array of metal-coordinating ligands adapted for coating other inorganic nanoparticles, including magnetic and plasmonic nanomaterials.


Performance Evaluation of STARPAM Polymer and Application in High Temperature and Salinity Reservoir.
Based on the properties of high temperature and salinity reservoir, the water-soluble polymer with good heat resistance and salt tolerance can be obtained through copolymerization between 2-acrylamide-2-methyl sulfonate monomer (AMPSN) and acrylamide monomer (AM) in water. The star shaped stable complexes (STARPAM) with the star nucleus of β-CD are prepared by living radical polymerization, which can improve the viscosity and change the percolation characteristics of the polymer in porous media. In the article, the performance of the STARPAM (star-shaped polymer) with heat resistance and salt tolerance was evaluated by comparing the viscosification property, heat and salt resistance, calcium and magnesium tolerance, and long-term thermal stability of STARPAM (star-shaped polymer) with those of HPAM (partially hydrolyzed polyacrylamide) and MO-4000 (linear polymer). The results of physical simulation experiment showed that the viscosity of the STARPAM is 3.3 times that of MO-4000 and 4 times that of HPAM under the conditions of mineralization degree of 20000 mg/L, concentration of 1500 mg/L, and 75°C, which indicated that heat resistance and salt tolerance of the STARPAM are excellent. Oil displacement experiments showed that STARPAM can enhance oil recovery by 20.53% after water flooding, and the effect of oil displacement is excellent. At present, 19 wells were effective with a ratio of 95.2%. Compared with before treatment, the daily liquid production increased by 136 m3, daily oil production increased by 44.6 t, water cut decreased by 4.67 percentage points, and flow pressure decreased by 1.15 MPa.


Immunogenicity of an accelerated vaccination regime with a combined hepatitis a/b vaccine in patients with chronic hepatitis C.
Hepatitis A (HAV) and B (HBV) vaccinations are recommended in patients with chronic liver diseases. We prospectively investigated immunogenicity and safety of an accelerated vaccination protocol (0-7-21 days) with the combined hepatitis A/B vaccine (Twinrix(R)) versus the standard vaccination scheme (0-1-6 months) in hepatitis C virus-infected patients versus healthy volunteers. Local and general symptoms were mostly mild in all groups. One month after completion of the accelerated vaccination or standard vaccination, with the combined hepatitis A/B vaccine anti-HAV seroconversion rates (>33 IU/l) were 89 % and 88 % in HCV-infected patients. Initial HCV-nonresponders developed protective anti-HAV antibodies in 94 % and 96 % after a booster dose. According to the anti-HBs seroprotection rate, HCV-infected patients developed protective anti-HBs titres (>10 IU/l) in 77 % and 82 % of cases one month after the accelerated and the standard vaccination scheme-at month 2 and 7, respectively. This anti-HBs seroprotection rate could even be increased to 84 % and 85 % when initial HCV-infected nonresponders where given a booster dose with the combined hepatitis A/B vaccine. Protective anti-HAV and anti-HBs titers were achieved as early as month 2 after the accelerated vaccination schedule in the majority of HCV-infected patients. Healthy subjects developed protective anti-HAV titers and anti-HBs titers in 100 % and 98 % after the accelerated and standard vaccination protocol. This study is the first to have demonstrated that the accelerated combined hepatitis A/B vaccination is both safe and highly immunogenic against HAV and HBV in HCV-infected patients with well compensated liver disease.


Transesophageal echocardiography and noncardiac surgery.
The use of transesophageal echocardiography (TEE) for monitoring during cardiac and noncardiac surgery has increased exponentially over the past few decades. TEE has evolved from a diagnostic tool to a monitoring device and a procedural adjunct. The close proximity of the TEE transducer to the heart generates high-quality images of the intracardiac structures and their spatial orientation. The use of TEE in noncardiac and critical care settings is not well studied, and the evidence of the benefits of its use in these settings is lacking. Despite the widespread availability of TEE equipment in US hospitals, less than 30% of anesthesiologists are formally trained in the use of perioperative TEE. In this review, the safety and indications of TEE are reviewed and detailed analysis of the best available evidence in this regard is presented. Landmark trials evaluating the use of TEE and its therapeutic impact in noncardiac surgical setting are critically reviewed. This article details recommendations to familiarize anesthesiologists with TEE technology to exploit it to its fullest potential to achieve better patient monitoring standards and eventually improve outcome. Training of greater numbers of anesthesiologists in TEE is needed to increase awareness of the indications and contraindications. Until relatively inexpensive TEE equipment is available, the initial cost of equipment acquisition remains a significant prohibitive factor limiting its widespread use.


Overlap in attitudes to policy measures on alcohol, tobacco and illegal drugs.
Effective alcohol, tobacco and illegal drug policies reduce the harm to users and third parties. Knowledge about determinants and interrelations between attitudes held by the general public to different types of policy measures can benefit policy-makers who aim to increase acceptance for effective policy. The present study describes the level of support for various policy measures held by the general public, and investigates the association between attitudes to policy measures on alcohol, tobacco and illegal drug. A sample of the Norwegian general population aged 16-64 (N=1803) was interviewed by telephone. Respondents reported demographic information, personal substance use and attitudes to various policy measures. Associations between attitudes were assessed with correlation and regression analysis. Associations between attitudes were strongest for similar policy measures across substance groups (e.g. tax increases on alcohol and tobacco). There was a weaker association between attitudes to different policy measures aimed at the same substance (e.g. tax increase on alcohol and campaigns on alcohol). The degree to which people approve or disapprove of the use of particular types of policy measures is irrespective of the targeted substance.


Autoimmune enteropathy with distinct mucosal features in T-cell activation deficiency: the contribution of T cells to the mucosal lesion.
Autoimmune enteropathy is normally characterised by crypt hyperplastic villous atrophy with enterocyte autoantibodies, activation of mucosal lymphocytes and increased epithelial HLA-DR. This case involved a severely affected Portuguese infant who was found to have lymphocyte activation deficiency and demonstrated correspondingly distinct mucosal features. A female infant of nonconsanguineous parents was treated for vomiting and diarrhoea, first with milk exclusion and then with parenteral nutrition. Lymphocyte subsets and immunoglobulin concentrations were normal, but in vitro testing showed no activation in response to phytohaemagglutinin, Candida, or purified protein derivative, although the response to interleukin (IL)-2 was intact. Interleukin-2 deficiency was excluded. Analysis of jejunal biopsy specimens revealed only mild villous blunting with absent goblet cells, normal epithelial proliferation, and no crypt hyperplasia. The dense infiltrate of CD8+ and CD4+ T lymphocytes showed normal CD2 and CD3 expression but no activation or proliferation markers. HLA-DR was not increased on epithelium or lymphocytes. Thus, in addition to in vitro evidence for lymphocyte activation deficiency, the mucosal specimens showed no evidence of in situ T-cell activation. After development of overwhelming septicaemia, the patient died at 18 months, just before a planned bone marrow transplant. These findings confirm significant heterogeneity within autoimmune enteropathy. Formal immune function testing should be performed in all affected infants to identify T-cell activation deficiencies. The distinct mucosal findings suggest that activated T cells usually induce the crypt hyperplastic villous atrophy characteristic of classic autoimmune enteropathy.


Some bifurcation methods of finding limit cycles.
In this paper we outline some methods of finding limit cycles for planar autonomous systems with small parameter perturbations. Three ways of studying Hopf bifurcations and the method of Melnikov functions in studying Poincare bifurcations are introduced briefly. A new method of stability- changing in studying homoclinic bifurcation is described along with some interesting applications to polynomial systems.


Respiratory Network Enhances the Sympathoinhibitory Component of Baroreflex of Rats Submitted to Chronic Intermittent Hypoxia.
Chronic intermittent hypoxia (CIH) produces respiratory-related sympathetic overactivity and hypertension in rats. In this study, we tested the hypothesis that the enhanced central respiratory modulation of sympathetic activity after CIH also decreases the sympathoinhibitory component of baroreflex of rats, which may contribute to the development of hypertension. Wistar rats were exposed to CIH or normoxia (control group) for 10 days. Phrenic nerve, thoracic sympathetic nerve, and neurons in the rostral ventrolateral medulla and caudal ventrolateral medulla were recorded in in situ preparations of rats. Baroreflex regulation of thoracic sympathetic nerve, rostral ventrolateral medulla, and caudal ventrolateral medulla neurons activities were evaluated in different phases of respiration in response to either aortic depressor nerve stimulation or pressure stimuli. CIH rats presented higher respiratory-related thoracic sympathetic nerve and rostral ventrolateral medulla presympathetic neurons activities at the end of expiration in relation to control rats, which are indexes of respiratory-related sympathetic overactivity. Baroreflex-evoked thoracic sympathetic nerve inhibition during expiration, but not during inspiration, was enhanced in CIH when compared with control rats. In addition, CIH selectively enhanced the expiratory-related baroreceptor inputs, probably through caudal ventrolateral medulla neurons, to the respiratory-modulated bulbospinal rostral ventrolateral medulla presympathetic neurons. These findings support the concept that the onset of hypertension, mediated by sympathetic overactivity, after 10 days of CIH is not secondary to a reduction in sympathoinhibitory component of baroreflex. Instead, it was observed an increase in the gain of sympathoinhibitory component in in situ preparations of rats, suggesting that changes in the respiratory-related sympathetic network after CIH also play a key role in preventing greater increase in arterial pressure.


Environmental risk of trace metals and metalloids in estuarine sediments: An example from Southampton Water, U.K.
Industrial and commercial port activities are widely recognized worldwide as an important source of pollution to proximal estuaries. In this study, we analysed geochemical and sedimentological parameters including major and trace elements, organic matter and sediment texture in surface sediments from the estuarine environment of Southampton Water, U.K. Using these data, and multivariate statistical tools [correlation, factor and cluster analysis and pollution indices such as Enrichment Factor (EF), Pollution Load Index (PLI) and the Adverse Effect Index (AEI)], we examine sedimentary trace metal and metalloid contamination, contamination sources, and potential biological impacts of the contamination present. The geochemical data, multivariate statistical analysis and pollution indices indicate that the spatial distribution of trace metals and metalloids is influenced by both sediment composition (and mixing) and anthropogenic activities. Most trace metal and metalloid concentrations are close to local geological background levels, except for Cu, Zn and Pb. The spatial distribution of these elements indicates that the Exxon oil refinery, Southampton port, local marinas and runoff from domestic and industrial activities act effectively as point sources of these elements. Pollution indices calculations highlight a degraded environment as a result of these pollutants, and further work is needed to assess the current impact of trace metals and metalloids on local ecology.


Earwax: A clue to discover fluoroacetate intoxication in cattle.
An innovative method was developed to detect fluoroacetate poisoning in cattle by headspace/gas chromatographic analysis of earwax samples of intoxicated cattle. Samples were collected from 2 groups of cattle subjected to induced fluoroacetate intoxication, each group receiving a different dose of acetamide (antidote). Monofluoroacetic acid was detected in samples of intoxicated cattle in concentrations inversely proportional to the dose of acetamide. Thus, earwax analysis represents a successful approach for detection and monitoring of fluoroacetate poisoning.


Clinical mass spectrometry in neuroscience. Proteomics and peptidomics.
In this review we discuss the merits and drawbacks with the use of proteomic and peptidomic strategies for identification of proteins and peptides in their multidimensional interactions in complex biological processes. The progress in proteomics and peptidomics during the last years offer us new challenges to study changes in the protein and peptide synthesis. These strategies also offer new tools to follow post-translational modifications and other disturbed chemical processes that may be indicative of pathophysiological alteration(s). Furthermore these techniques can contribute to improvements in the diagnosis and therapy of neurodegenerative diseases, such as Alzheimer's disease, and psychiatric diseases, as depression and post traumatic stress disorders. We also consider different practical aspects of the applications of mass spectrometry in clinical neuroscience, illustrated by example from our laboratories. The new proteomic and peptidomic strategies will further enable the progress for clinical neuroscience research.


Enhanced expression in tobacco of the gene encoding green fluorescent protein by modification of its codon usage.
The gene encoding green fluorescent protein (GFP) from Aequorea victoria was resynthesized to adapt its codon usage for expression in plants by increasing the frequency of codons with a C or a G in the third position from 32 to 60%. The strategy for constructing the synthetic gfp gene was based on the overlap extension PCR method using 12 long oligonucleotides as the starting material and as primers. The new gene contains 101 silent nucleotide changes compared to its wild-type counterpart used in this study. Several transgenic tobacco lines containing the wild-type gfp gene contained minute amounts of a smaller protein cross-reacting with GFP antiserum, whereas only one protein of the expected size was found in transgenics with the synthetic gfp gene. The smaller protein was probably encoded by a truncated gfp mRNA created by splicing of a 84 bp cryptic intron as detected by a reverse transcription-PCR technique. A comparison of GFP production in transgenics with the wild-type and the synthetic gfp gene under the control of the enhanced CaMV 35S promoter showed that the large-scale alterations in the gfp gene increased the frequency of high expressors in the transgenic population but hardly changed the maximum GFP concentrations. The latter phenomenon may be attributed to a reduced regeneration capacity of transformed cells with higher GFP concentrations.


Continuous irradiation and flash-photolysis studies of new[3H]naphtho[2,1-b]pyrans linked by covalent bonds to oligothiophene units. Effect of thiophene substituents on the photochromism.
The influence of oligothiophene substituents on five new [3H]naphtho[2,1-b]pyrans has been investigated using flash photolysis and continuous irradiation techniques. Photochromic properties strongly depend on the number and position of the thienyl units. Thienyl substitution increases the UV/visible absorbance of the lower energy transition of both the naphthopyran and merocyanine isomers. The rate constants of the thermal fading processes also increase with the number of thiophenic entities. Although several minor photoisomers, whose relative amounts depend on the irradiation conditions could be involved, it has been assumed that under continuous monochromatic irradiation, the evolution of the photochromic reaction can be described by the formation of only one photoisomer. Under these conditions, quantum yields of photocolouration and molar absorption coefficients of the non-isolable photomerocyanine isomer were evaluated by photokinetic analysis. Flash-photolytic colourability can be interpreted using continuous irradiation parameters. A linear correlation has been established between experimental and calculated colourability. This result shows that similar photochromic reactions leading to similar photoisomers are triggered either by polychromatic flash photolysis or by continuous monochromatic irradiation.


High Fat Diet-induced Breast Cancer Model in Rat.
Obesity has been linked to breast cancer progression but the underlying mechanisms remain obscure. Being overweight or obese for a woman at the time she is diagnosed with breast cancer is linked to a high risk of recurrence regardless of treatment factors. In rodents, high body weight is also associated with increased incidence of spontaneous and chemically induced tumors. To study the complex interaction between the mammary epithelia and the microenvironment, with a focus on the mechanism underlying the role obesity plays in the regulation of the cancer stem cell traits and the development of mammary cancer in vivo, we have established a diet-induced obesity (DIO) rat model of breast cancer (Chang et al., 2015).


Influence of vegetation on the spatial distribution of Toxorhynchites moctezuma ovipositions in the field.
The influence of the vegetation surrounding black-painted calabash ovitraps on the number of eggs of the mosquito Toxorhynchites moctezuma they attracted was investigated using oviposition data gathered from a seasonal-deciduous forest in Trinidad, West Indies. More eggs were laid into ovitraps situated either within or directly adjacent to trees or bamboo stools than those not associated with trees or bamboo. This result is discussed in terms of the initial oviposition-site searching behavior of female Toxorhynchites.


[A study on the ultrastructure of plant cell under simulated microgravity].
To study the effects of microgravity on plant cell ultrastructure. Analyzing the biological and physiological differences between the plants grown in the simulated microgravity conditions and their correspondent ground controls. Various variances in cell walls, chloroplasts and mitochondria were observed with electron microscope. Those ultrastructure changes included plasmolysis, twist, contraction and deformation of cell walls, curvature and loose arrangement of chloroplast lamellae, breach of mitochondria, overflow of inclusions, disappearance of cristae, and significant increase in number of starch grains per cell. Simulated microgravity conditions exert some coerce influence on the plant growth and the changes above-mentioned were the responses in cell level.


Circadian clock as a possible control point in colorectal cancer progression (Review).
The circadian rhythm is generated at the cellular level by a molecular clock system that involves specific genes. Studies have revealed that circadian clock disruption is a control point in cancer progression. Colorectal cancer (CRC) is one of the cancers closely associated with circadian disruption. In the present review, the involvement of the circadian clock in CRC development was summarized. Abnormal expression of certain clock genes has been found in patients with CRC and their correlation with clinicopathological features has also been explored. The period and cryptochrome 2 (Cry2), Sirtuin1 (SIRT1) and neuronal PAS domain protein 2 (NPAS2) genes were reported to have tumour suppressor properties. Conversely, Cry1, brain and muscle ARNT‑like‑1, circadian locomotor output cycles kaput (CLOCK) and timeless may aggravate CRC progression, but these findings are not consistent and require to be confirmed by further research. Circadian scheduling also indicated advantages in chemotherapy treatments for patients with CRC by increasing the maximum tolerated doses and decreasing toxicities. Dysfunction of the molecular CLOCK system disrupted cellular processes to accelerate colon tumorigenesis, such as metabolism, cell cycle, DNA damage repair, proliferation and apoptosis, epithelial‑mesenchymal transition and stemness. The clock gene network and how the dynamics of the system influence CRC were discussed.


Chemotherapy Can Synergize With Adoptive Immunotherapy to Inhibit Medulloblastoma Growth.
In the age of ever-increasing developments in targeted cancer treatments, new immune-based approaches for brain tumor therapy represent an attractive avenue. Despite encouraging pre-clinical data, results in patients have been sub-optimal, likely due to tumor-induced immune suppression and intrinsic resistance to immune attack. Chemotherapy and biologic agents may be able to disrupt these mechanisms and restore tumor sensitivity to immune attack. In this study, we explore whether a combination of gemcitabine and rapamycin can sensitize medulloblastoma cells to immunotherapy in vitro and in vivo. With the commercial medulloblastoma cell line, Daoy, we explored the concentrations of combinations of Gemcitabine with rapamycin needed to induce cytotoxicity. Next, we used flow cytometry to assess the cytotoxicity of chemotherapy-treated Daoy cells with the addition of anti-tumor T-cells, generated from naive T-cells stimulated in the presence of Daoy lysate-pulsed dendritic cells. Then, we examined the efficacy of chemotherapy alone versus chemotherapy plus immunotherapy in tumor growth inhibition of subcutaneous medulloblastoma xenografts. Rapamycin alone at <1,000 nM had moderate activity against Daoy cells in vitro and IC50 was >1,000 nM. Gemcitabine had a 3-day IC50 alone of 10 nM but in combination with 100 nM rapamycin, it decreased to 1 nM, suggesting increased cytotoxicity with combined therapy. Stimulated T-cells mediated in-vitro cytotoxicity, although background cytotoxicity of unstimulated "naïve" T-cells was also significant. Finally, established subcutaneous Daoy cell xenografts in SCID mice were treated with chemotherapy alone or chemotherapy plus adoptive immunotherapy (stimulated and non-stimulated). Gemcitabine and rapamycin alone significantly slowed tumor growth, but the addition of immunotherapy further augmented inhibition. Combining immunotherapy and chemo-biologic therapy inhibit medulloblastoma cell and xenograft growth, and may offer an effective treatment for patients with medulloblastoma.


The effect of quercetin on microRNA expression: A critical review.
Quercetin, a flavonoid with multiple proven health benefits to both man and animals, displays a plethora of biological activities, collectively referred to as pleiotropic. The most studied of these are antioxidant and anti-inflammatory but modulation of signalling pathways is important as well. One of the lesser-known and recently discovered roles of quercetin, is modulation of microRNA (miRNA) expression. miRNAs are important posttranscriptional modulators that play a critical role in health and disease and many of these non-coding oligonucleotides are recognized as oncogenic or tumor suppressor miRNAs. This review is an evaluation of the recent relevant literature on the subject, with focus on the ability of quercetin to modulate miRNA expression. It includes a summary of recent knowledge on miRNAs deregulated by quercetin, an overview of quercetin pharmacokinetics and miRNA biogenesis, for the interested reader.


Multinuclear NMR and kinetic analysis of DNA interstrand cross-link formation.
Recently, a phenylselenyl-modified thymidine (2) was shown to produce DNA interstrand cross-links (ICLs) via two mechanisms. Photolysis of 2 generates 5-(2'-deoxyuridinyl)methyl radical (1), the reactive intermediate that results from formal hydrogen atom abstraction from the thymine methyl group. This reactive intermediate reacts with the opposing dA and is the first example of a DNA radical that produces ICLs. Kinetic competition studies support the proposal that the rate-limiting step in ICL formation from 1 involves rotation about the glycosidic bond and that the rate constant for this process is influenced by the flanking sequence. Cross-links also form with the opposing dA when 2 is treated with mild oxidants that result in the formation of an intermediate methide-like species (4). Kinetic experiments reveal that 4 reacts with azide, a model nucleophile, via an S(N)2' pathway. Previous experiments suggested that the same product is produced via 1 or 4 but that the initially formed cross-link rearranges during the enzyme digestion and isolation procedures. In situ product analysis by NMR using synthetic, doubly labeled duplex DNA containing (13)C-2 and (15)N(1)-dA provides definitive evidence that the kinetic ICL products formed via the radical and oxidative pathways are the same and correspond to that arising from formal alkylation of N(1)-dA. Furthermore, analysis of the thermodynamic product formed upon rearrangement indicates that the primary product isomerizes via an associative mechanism in DNA.


Flt-1-dependent survival characterizes the epithelial-mesenchymal transition of colonic organoids.
Aberrant cell survival and resistance to apoptosis are hallmarks of tumor invasion and progression to metastatic disease, but the mechanisms involved are poorly understood. The epithelial-mesenchymal transition (EMT), a process that facilitates progression to invasive cancer, provides a superb model for studying such survival mechanisms. Here, we used a unique spheroid culture system that recapitulates the structure of the colonic epithelium and undergoes an EMT in response to cytokine stimulation to study this problem. Our data reveal that the EMT results in the increased expression of both VEGF and Flt-1, a tyrosine kinase VEGF receptor, and that the survival of these cells depends on a VEGF/Flt-1 autocrine pathway. Perturbation of Flt-1 function by either a blocking antibody or adenoviral expression of soluble Flt-1, which acts in a dominant-negative fashion, caused massive apoptosis only in cells that underwent EMT. This pathway was critical for the survival of other invasive colon carcinoma cell lines, and we observed a correlative upregulation of Flt-1 expression linked to in vivo human cancer progression. A role for Flt-1 in cell survival is unprecedented and has significant implications for Flt-1 function in tumor progression, as well as in other biological processes, including angiogenesis and development.


Microparticulate Caspase 1 Regulates Gasdermin D and Pulmonary Vascular Endothelial Cell Injury.
Lung endothelial cell apoptosis and injury occur throughout all stages of acute lung injury/acute respiratory distress syndrome and impact disease progression. Caspases 1, 4, and 5 are essential for completion of the apoptotic program known as pyroptosis that also involves proinflammatory cytokines. Because gasdermin D (GSDMD) mediates pyroptotic death and is essential for pore formation, we hypothesized that it might direct caspase 1-encapsulated microparticle (MP) release and mediate endothelial cell death. Our present work provides evidence that GSDMD is released by LPS-stimulated THP-1 monocytic cells, where it is packaged into microparticles together with active caspase 1. Furthermore, only MP released from stimulated monocytic cells that contain both cleaved GSDMD and active caspase 1 induce endothelial cell apoptosis. MPs pretreated with caspase 1 inhibitor Y-VAD or pan-caspase inhibitor Z-VAD do not contain cleaved GSDMD. MPs from caspase 1-knockout cells are also deficient in p30 active GSDMD, further confirming that caspase 1 regulates GSDMD function. Although control MPs contained cleaved GSDMD without caspase 1, these fractions were unable to induce cell death, suggesting that encapsulation of both caspase 1 and GSDMD is essential for cell death induction. Release of microparticulate active caspase 1 was abrogated in GSDMD knockout cells, although cytosolic caspase 1 activation was not impaired. Last, higher concentrations of microparticulate GSDMD were detected in the plasma of septic patients with acute respiratory distress syndrome than in that of healthy donors. Taken together, these findings suggest that GSDMD regulates the release of microparticulate active caspase 1 from monocytes essential for induction of cell death and thereby may play a critical role in sepsis-induced endothelial cell injury.


[Effects of different ecological conditions on grain quality and RVA profile of japonica rice from Yunnan of China and Korea].
Taking sixteen japonica rice varieties from Yunnan of China and Korea growing at three locations with different altitudes in Yunnan Plateau as test materials, this paper studied the effects of different ecological conditions on their grain quality, including brown rice length (BRL), brown rice width (BRW), length-width ratio (L/W), chalky rate (CR), whiteness (WH), amylose content (AC), protein content (PC), and alkali digestion value (ADV), and their starch RVA profile, including peak viscosity (PKV), hot viscosity (HTV), final viscosity (FLV), breakdown viscosity (BDV), setback viscosity (SBV), consistence viscosity( CTV), peak time (PeT), and pasting temperature (PaT). Of all the test parameters, SBV had the largest coefficient of variation. The coefficients of variation of BRL, CR, AC, PC, ADV, FLV, SBV, and PeT of Yunnan varieties were higher than those of Korean varieties, while the BRW, L/W, WH, PKV, HTV, BDV, CTV, and PaT of Korean varieties had higher coefficients of variation than those of Yunnan varieties. With increasing altitude, the BRL, BRW, L/W, WH, AC, ADV, FLV, and CTV of Yunnan varieties, and the BRL, BRW, WH, PC, PKV, HTV and BDV of Korean varieties decreased significantly, while the CR, PC, HTV, and PeT of Yunnan varieties, and the L/W, AC, ADV, SBV and CTV of Korean varieties increased significantly. The CR of Korean varieties had no obvious change. The PKV, BDV, and PaT of Yunnan varieties and the PaT of Korean varieties increased after an initial decrease, whereas the SBV of Yunnan varieties and the FLV and PeT of Korean varieties were in reverse.


Proinflammatory CXCL12-CXCR4/CXCR7 Signaling Axis Drives Myc-Induced Prostate Cancer in Obese Mice.
Obesity is a prognostic risk factor in the progression of prostate cancer; however, the molecular mechanisms involved are unclear. In this study, we provide preclinical proof of concept for the role of a proinflammatory CXCL12-CXCR4/CXCR7 signaling axis in an obesity-driven mouse model of myc-induced prostate cancer. Analysis of the stromal vascular fraction from periprostatic white adipose tissue from obese HiMyc mice at 6 months of age revealed a dramatic increase in mRNAs encoding various chemokines, cytokines, growth factors, and angiogenesis mediators, with CXCL12 among the most significantly upregulated genes. Immunofluorescence staining of ventral prostate tissue from obese HiMyc mice revealed high levels of CXCL12 in the stromal compartment as well as high staining for CXCR4 and CXCR7 in the epithelial compartment of tumors. Prostate cancer cell lines derived from HiMyc tumors (HMVP2 and derivative cell lines) displayed increased protein expression of both CXCR4 and CXCR7 compared with protein lysates from a nontumorigenic prostate epithelial cell line (NMVP cells). CXCL12 treatment stimulated migration and invasion of HMVP2 cells but not NMVP cells. These effects of CXCL12 on HMVP2 cells were inhibited by the CXCR4 antagonist AMD3100 as well as knockdown of either CXCR4 or CXCR7. CXCL12 treatment also produced rapid activation of STAT3, NFκB, and MAPK signaling in HMVP2 cells, which was again attenuated by either AMD3100 or knockdown of CXCR4 or CXCR7. Collectively, these data suggest that CXCL12 secreted by stromal cells activates invasiveness of prostate cancer cells and may play a role in driving tumor progression in obesity. Targeting the CXCL12-CXCR4/CXCR7 axis could lead to novel approaches for offsetting the effects of obesity on prostate cancer progression. Cancer Res; 77(18); 5158-68. ©2017 AACR.


FRET excited ratiometric oxygen sensing in living tissue.
Dynamic analysis of oxygen (O₂) has been limited by the lack of a real-time, quantitative, and biocompatible sensor. To address these demands, we designed a ratiometric optode matrix consisting of the phosphorescence quenching dye platinum (II) octaethylporphine ketone (PtOEPK) and nanocystal quantum dots (NQDs), which when embedded within an inert polymer matrix allows long-term pre-designed excitation through fluorescence resonance energy transfer (FRET). Depositing this matrix on various glass substrates allowed the development of a series of optical sensors able to measure interstitial oxygen concentration [O₂] with several hundred millisecond temporal resolution in varying biological microdomains of active brain tissue.


Horizontal gene transfer of chlamydial-like tRNA genes into early vascular plant mitochondria.
Mitochondrial genomes of lycophytes are surprisingly diverse, including strikingly different transfer RNA (tRNA) gene complements: No mitochondrial tRNA genes are present in the spikemoss Selaginella moellendorffii, whereas 26 tRNAs are encoded in the chondrome of the clubmoss Huperzia squarrosa. Reinvestigating the latter we found that trnL(gag) and trnS(gga) had never before been identified in any other land plant mitochondrial DNA. Sensitive sequence comparisons showed these two tRNAs as well as trnN(guu) and trnS(gcu) to be very similar to their respective counterparts in chlamydial bacteria. We identified homologs of these chlamydial-type tRNAs also in other lycophyte, fern, and gymnosperm DNAs, suggesting horizontal gene transfer (HGT) into mitochondria in the early vascular plant stem lineages. These findings extend plant mitochondrial HGT to affect individual tRNA genes, to include bacterial donors, and suggest that Chlamydiae on top of their recently proposed key role in primary chloroplast establishment may also have participated in early tracheophyte genome evolution.


Pretreatment of Siam weed stem by several chemical methods for increasing the enzymatic digestibility.
Siam weed [Chromolaena odorata (L.) King & Robinson], an invasive exotic weed in China, was proposed as a feedstock for bioethanol production. This would be a promising way of using for an invasive weed that needs management and control. It was found that the glucan content of the weed stem was similar to that of sugarcane bagasse, but higher than those of corn stover and wheat straw. Several chemical pretreatment methods were applied to the weed stem to increase its enzymatic digestibility. Mild sulfuric acid (<120 degrees C) or alkali pretreatment did not markedly increase the enzymatic digestibility. However, peracetic acid (PAA) pretreatment dramatically enhanced the enzymatic hydrolysis of the weed stem. Compared to some other common agricultural residues, the weed stem was more difficult to pretreat and digest by cellulase. Fourier transform infrared (FTIR) spectra analysis indicated that the cellulose-related bands became more intensive after pretreatment, especially for PAA-pretreated samples. According to X-ray diffraction spectra, the biomass solids had higher crystallinity indices after pretreatment, although these indices were similar for all of the pretreated samples.


Differences of the reconstructed stature in an early Medieval population depending on Pearson's regression equations.
On the basis of 238 male and 230 female skeletons, derived from a Medieval cemetery from Gruczno, Northern Poland, limb bones' proportion was determined. Substantial differences (d > 1 standard deviation) were established in 30% of the individuals, which, according to the relative relations among the separate bones, were divided into 6 groups. For separate individuals of each group a body height was calculated on the basis of Pearson's regression equation (Rösing 1988) as well as separately their arithmetic means for single limb bones and for two bones. The analysis of the absolute differences (the average and maximum values) among all the reconstructed body heights show that the calculated body height depends on the limb proportion. The degree oft the dependence does not seem to depend on the limb proportion group because the most significant differences for both sexes are connected with other proportion groups. The differences in the reconstructed body height are larger for the female skeletons.


A novel ketoconazole bioadhesive effervescent tablet for vaginal delivery: design, in vitro and 'in vivo' evaluation.
Bioadhesive tablet formulations of ketoconazole for vaginal delivery were studied. Carbomer (Carbopol 974P, Carbopol 934P), hydroxypropylmethyl cellulose (HPMC) and hydroxypropyl cellulose (HPC) were used as candidate bioadhesive polymers. Effervescent was incorporated into the formulations as a disintegration agent. The swelling behavior and bioadhesive strength of the drug-free tablets were investigated. Carbopol 934P was selected as biopolymer in combination with HPMC or HPC at different ratios to develop five drug-loaded formulations. The swellings, tackiness and in vitro release were studied on the tablets. A good sustained effect and a moderate bioadhesion were obtained with the tablets. The formulation containing 100mg of effervescent, with the Carbopol 934P:HPC ratio of 1:9, seemed to be the optimum one for the tablet. In vivo drug residence tests were carried out by administering the preferred formulation to female rats. The results showed that the drug remaining followed a one-order model. Even after 24h of administration in vagina of rats, 17% of the original employed drug was retained on the vaginal tissue. Our study may provide a potential vaginal tablet formulation of ketoconazole against Candida albicans.


Gamma-tubulin complexes and microtubule organization.
Microtubule nucleation requires gamma-tubulin, which exists in two main protein complexes: the gamma-tubulin small complex, and the gamma-tubulin ring complex. During mitosis, these complexes accumulate at the centrosome to support spindle formation. Gamma-tubulin complexes are also present at non-centrosomal microtubule nucleation sites, both in interphase and in mitosis. In interphase, non-centrosomal nucleation enables the formation of microtubule bundles or networks of branched microtubules. Gamma-tubulin complexes may be involved not only in microtubule nucleation, but also in regulating microtubule dynamics. Recent findings indicate that the dynamics of microtubule plus-ends are altered, depending on the expression of gamma-tubulin complex proteins.


Non-hormone chemotherapy for prostate cancer: principles of treatment and application to the testing of new drugs.
Prostate cancer, one of the commonest malignancies in western society, remains a major challenge in management. Although the typical patient is elderly and may not withstand aggressive approaches to treatment, increasing numbers of our population survive to old age, while remaining healthy and active. As prostate cancer is a disease of old age, it is therefore likely that there will be an increased requirement to combat this disease in a fit patient population. Although hormonal manipulation provides effective first-line treatment for 70%-80% of patients with metastatic disease, the majority of these ultimately relapse. Cytotoxic chemotherapy has not provided a panacea for relapsed, hormone-resistant prostate cancer. Despite the significant subjective and objective responses that can be achieved by the use of single agents, the median survival of patients with hormone-resistant disease remains less than 12 months. The use of combination cytotoxic regimens has not altered this. New approaches, perhaps including the development of new cytotoxic agents, innovative uses of established drugs, or the application of the biological response modifiers will be required before this problem is resolved. Until then, we must not be satisfied with inadequate indices of success. The reporting of response rates and of survival statistics drawn from the small group of responding patients is no true indicator of success. Until truly effective treatment is available, we must learn to define more useful indicators of patient benefit, to be more effective in palliating the symptoms of this disease, and to be more critical of the limitations of our progress.