Hsa_circ_0020095 Promotes Oncogenesis and Cisplatin Resistance in Colon Cancer by Sponging miR-487a-3p and Modulating SOX9.
Colon cancer (CC) currently ranks as the third most common human cancer worldwide with an increasing incidence and a poor prognosis. Recently, circular RNAs have been reported to regulate the progression of diverse human cancers. However, the role of circRNA hsa_circ_0020095 in CC remains largely unclear. Expression levels of the related circRNAs, microRNAs and mRNA in CC tissues and cells were determined. The impacts of circ_0020095 or miR-487a-3p on CC cells were examined at the indicated times after transfection. Meanwhile, a luciferase-reporter experiment was employed to validate the interplay between miR-487a-3p and circ_002009695 or SOX9. Moreover, the in vivo tumor growth assay was applied to further evaluate the effects of circ_0020095 knockdown on CC progression. We demonstrated that circ_0020095 was highly expressed in CC tissues and cells. The proliferation, migration, invasion, and cisplatin resistance of CC were suppressed by silencing circ_0020095 in vitro and in vivo or by ectopic expression of miR-487a-3p in vitro. Mechanistically, circ_0020095 could directly bind to miR-487a-3p and subsequently act as a miR-487a-3p sponge to modulate the activity by targeting the 3'-UTR of SOX9. Interestingly, overexpression of circ_0020095 dramatically reversed the suppressive effects of miR-487a-3p mimics on CC cells. Circ_0020095 functions as an oncogene to accelerate CC cell proliferation, invasion, migration and cisplatin resistance through the miR-487a-3p/SOX9 axis, which could be a promising target for CC treatment.


Repetitive transcranial magnetic stimulation as an alternative therapy for dysphagia after stroke: a systematic review and meta-analysis.
A meta-analysis and systematic review was conducted to investigate the potential effects of repetitive transcranial magnetic stimulation on dysphagia in patients with stroke, including different parameters of frequency and stimulation site. PubMed, Embase, MEDLINE databases and the Cochrane Library, were searched for randomized controlled studies of repetitive transcranial magnetic stimulation treatment of dysphagia published before March 2016. Six clinical randomized controlled studies of a total of 163 stroke patients were included in this meta-analysis. A significant effect size of 1.24 was found for dysphagic outcome (mean effect size, 1.24; 95% confidence interval (CI), 0.67-1.81). A subgroup analysis based on frequency showed that the clinical scores were significantly improved in dysphagic patients with low frequency repetitive transcranial magnetic stimulation treatment ( P < 0.05) as well as high frequency repetitive transcranial magnetic stimulation treatment ( P < 0.05). A stimulation site stratified subgroup analysis implied significant changes in stroke patients with dysphagia for the unaffected hemisphere ( P < 0.05) and the bilateral hemisphere stimulation ( P < 0.05), but not for the affected hemisphere ( P > 0.05). The analysis of the follow-up data shows that patients in the repetitive transcranial magnetic stimulation groups still maintained the therapeutic benefit of repetitive transcranial magnetic stimulation four weeks after the last session of repetitive transcranial magnetic stimulation therapy ( P < 0.05). This meta-analysis indicates that repetitive transcranial magnetic stimulation has a positive effect on dysphagia after stroke. Compared with low-frequency repetitive transcranial magnetic stimulation, high-frequency repetitive transcranial magnetic stimulation may be more beneficial to the patients. This meta-analysis also supports that repetitive transcranial magnetic stimulation on an unaffected - or bilateral - hemisphere has a significant therapeutic effect on dysphagia.


Children and Medicaid: the experience in four states.
Medicaid coverage of children is analyzed in this article, using data from uniform Medicaid files (Tape-to-Tape) for California, Georgia, Michigan, and New York. Results show that Medicaid is a different program to children of different enrollment groups and ages. For children receiving cash assistance through either Aid to Families with Dependent Children or Supplemental Security Income, Medicaid represents a source of ongoing health coverage. However, for children in families not receiving cash assistance, coverage is more episodic and disproportionately related to acute care and hospitalization. Across all child enrollment groups, infants had higher than expected utilization and expenditures.


Lower Interstitial Glucose Concentrations but Higher Glucose Variability during Low-Energy Diet Compared to Regular Diet-An Observational Study in Females with Obesity.
This is an observational study of interstitial glucose (IG) concentrations, IG variability and dietary intake under free-living conditions in 46 females with obesity but without diabetes. We used continuous glucose monitoring, open-ended food recording and step monitoring during regular dietary intake followed by a low-energy diet (LED). Thirty-nine participants completed both study periods. The mean BMI at baseline was 43.6 ± 6.2 kg/m2. Three weeks of LED resulted in a mean weight loss of 5.2% with a significant reduction in diurnal IG concentration but with greater glycemic variability observed during LED. The mean 24 h IG concentration decreased from 5.8 ± 0.5 mmol/L during the regular diet period to 5.4 ± 0.5 mmol/L (p < 0.001) during LED, while the mean amplitude of glycemic excursion increased from 1.5 ± 0.7 to 1.7 ± 0.7 mmol/L (p = 0.031). The positive incremental area under the curve at breakfast was significantly larger for LED compared to regular diet. The daily fiber intake and the glycemic index of breakfast meals were significantly associated with the glycemic variability during regular dietary intake. In conclusion, the 24 h mean IG concentration was lower but with more pronounced glycemic variability during LED compared to a regular diet.


Totally laparoscopic total gastrectomy for locally advanced middle-upper-third gastric cancer.
Totally laparoscopic total gastrectomy (TLTG) for locally advanced middle-upper-third gastric cancer is becoming increasingly popular. The difficulty of TLTG for locally advanced middle-upper-third gastric cancer is laparoscopic spleen-preserving splenic hilar lymphadenectomy and the intracorporeal digestive tract reconstruction. We summed up a set of unique experience through clinical practice to simplify operation procedures. We performed TLTG with Huang's three-step maneuver in laparoscopic spleen-preserving splenic hilar lymphadenectomy and a later-cut overlap Roux-en-Y anastomosis in the intracorporeal digestive tract reconstruction for patients with locally advanced middle-upper-third gastric cancer. The Huang's three-step maneuver divided the complicated procedure of laparoscopic spleen-preserving splenic hilar lymphadenectomy into three steps, including the dissection of the lymph nodes (LNs) in the inferior pole region of the spleen (1st step), the region of the splenic artery trunk (2nd step), and the superior pole region of the spleen (3rd step). The later-cut overlap Roux-en-Y anastomosis used only endoscopic linear staplers intracorporeally and the small intestine was cut off after the esophagojejunostomy was completed, so that we could grasp the small intestine more easily and determine the direction of anastomosis more conveniently. One patient experienced later anastomotic leakage and was successfully treated by conservative in 16 consecutive patients. No patient experienced any operation-related complications. At a median follow-up of 15 months, no patients had died or experienced recurrent or metastatic disease. TLTG with Huang's three-step maneuver in laparoscopic spleen-preserving splenic hilar lymphadenectomy and a later-cut overlap Roux-en-Y anastomosis in the intracorporeal digestive tract reconstruction for locally advanced middle-upper-third gastric cancer was technically safe and feasible, with acceptable short-term outcomes.


Identification and extraction of proteins that compose the triad junction of skeletal muscle.
Treatment of both transverse tubules and terminal cisternae with a combination of Triton X-100 and hypertonic K cacodylate causes dissolution of nonjunctional proteins and selective retention of membrane fragments which are capable of junction formation. Treatment of vesicles with Triton X-100 and either KCl or K gluconate causes complete dissolution of all components. Therefore K cacodylate exerts a specific preservative action on the junctional material. The membrane fragment from treatment of transverse tubules with Triton X-100 + cacodylate contains a protein of Mr = 80,000 in SDS gel electrophoresis as the predominant protein while lipid composition is enriched in cholesterol. The membrane fragment retains in electron microscopy the trilaminar appearance of the intact vesicles. Freeze fracture of transverse tubule fragments reveals a high density of low-profile, intercalated particles, which frequently form strings or occasional small arrays. The fragments from Triton X-100 plus cacodylate treatment of terminal cisternae include the protein of Mr = 80,000 as well as the spanning protein of the triad, calsequestrin, and some minor proteins. The fragments are almost devoid of lipid and display an amorphous morphology suggesting membrane disruption. The ability of the transverse tubular fragment, which contains predominantly the Mr = 80,000 protein, to form junctions with terminal cisternae fragments suggests that it plays a role in anchoring the membrane to the junctional processes of the triad. The junctional proteins may be solubilized in a combination of nonionic detergent and hypertonic NaCl. Subsequent molecular sieve chromatography gives an enriched preparation of the spanning protein. This protein has subunits of Mr = 300,000, 270,000 and 140,000 and migrates in the gel as a protein of Mr = 1.2 X 10(6) indicating a polymeric structure.


Transcutaneous delivery of mung bean-derived nanoparticles for amelioration of psoriasis-like skin inflammation.
Psoriasis is a complex autoimmune disease that is closely associated with the disorganized pro-inflammatory polarization of macrophages and the activation of inflammatory signalling pathways. Nanoparticles (NPs) have shown their potential in immune response regulation and the related treatment of inflammatory diseases. Herein, we report the modulation of the skin immune system for amelioration of psoriasis-like skin inflammation using mung bean-derived NPs (MBNs), which exhibit high antioxidant activity to reduce reactive oxygen species (ROS) and modulate the immune microenvironment. For imiquimod (IMQ)-stimulated psoriasis-like skin, topical administration of MBNs can achieve the homeostasis of polarized macrophages and antagonize the activation of the nuclear factor kappa B (NF-κB) signalling pathway, which result in the alleviation of skin inflammation. The transcutaneous delivery of MBNs provides a promising approach for the treatment of psoriasis and other inflammatory skin diseases.


SH003 selectively induces p73‑dependent apoptosis in triple‑negative breast cancer cells.
Triple-negative breast cancer (TNBC) is a breast cancer subtype that has an aggressive phenotype, is highly metastatic, has limited treatment options and is associated with a poor prognosis. In addition, metastatic TNBC has no preferred standard chemotherapy due to resistance to anthracyclines and taxanes. The present study demonstrated that a herbal extract, SH003, reduced cell viability and induced apoptosis in TNBC without cell cytotoxicity. Cell viability was examined using trypan blue exclusion and colony formation assays, which revealed a decrease in the cell viability. Additionally, apoptosis was determined using flow cytometry and a sub‑G1 assay, which revealed an increase in the proportion of cells in the sub‑G1 phase. The present study investigated the anticancer effect of SH003 in the Hs578T, MDA‑MB‑231 and ZR‑751 TNBC cell lines, and in the MCF7 and T47D non‑TNBC cell lines. Western blot analysis revealed that the expression levels of poly‑ADP‑ribose polymerase (PARP) cleavage protein in cells treated with SH003 were increased dose‑dependent manner, indicating that SH003 induced apoptosis via a caspase‑dependent pathway. Pre‑treatment with the caspase inhibitor Z‑VAD reduced SH003‑induced apoptosis was examined using trypan blue exclusion. Moreover, SH003 treatment enhanced the p73 levels in MDA‑MB‑231 cells but not in MCF7 cells. Transfection of p73 small interfering RNA (siRNA) in MDA‑MB0231 cells revealed that the apoptotic cell death induced by SH003 was significantly impaired in comparison with scramble siRNA transfected MDA‑MB‑231 cells. This was examined using trypan blue exclusion and flow cytometry analysis (sub‑G1). In addition, SH003 and paclitaxel exhibited synergistic anticancer effects on TNBC cells. The results indicate that SH003 exerts its anticancer effect via p73 protein induction and exhibits synergistic anticancer effects when combined with paclitaxel.


Inflammasome and Its Therapeutic Targeting in Rheumatoid Arthritis.
Inflammasome is a cytoplasmic multiprotein complex that facilitates the clearance of exogenous microorganisms or the recognition of endogenous danger signals, which is critically involved in innate inflammatory response. Excessive or abnormal activation of inflammasomes has been shown to contribute to the development of various diseases including autoimmune diseases, neurodegenerative changes, and cancers. Rheumatoid arthritis (RA) is a chronic and complex autoimmune disease, in which inflammasome activation plays a pivotal role in immune dysregulation and joint inflammation. This review summarizes recent findings on inflammasome activation and its effector mechanisms in the pathogenesis of RA and potential development of therapeutic targeting of inflammasome for the immunotherapy of RA.


G-quadruplex formation within the promoter of the KRAS proto-oncogene and its effect on transcription.
In human and mouse, the promoter of the KRAS gene contains a nuclease hypersensitive polypurine-polypyrimidine element (NHPPE) that is essential for transcription. An interesting feature of the polypurine G-rich strand of NHPPE is its ability to assume an unusual DNA structure that, according to circular dichroism (CD) and DMS footprinting experiments, is attributed to an intramolecular parallel G-quadruplex, consisting of three G-tetrads and three loops. The human and mouse KRAS NHPPE G-rich strands display melting temperature of 64 and 73 degrees C, respectively, as well as a K+-dependent capacity to arrest DNA polymerase. Photocleavage and CD experiments showed that the cationic porphyrin TMPyP4 stacks to the external G-tetrads of the KRAS quadruplexes, increasing the T(m) by approximately 20 degrees C. These findings raise the intriguing question that the G-quadruplex formed within the NHPPE of KRAS may be involved in the regulation of transcription. Indeed, transfection experiments showed that the activity of the mouse KRAS promoter is reduced to 20% of control, in the presence of the quadruplex-stabilizing TMPyP4. In addition, we found that G-rich oligonucleotides mimicking the KRAS quadruplex, but not the corresponding 4-base mutant sequences or oligonucleotides forming quadruplexes with different structures, competed with the NHPPE duplex for binding to nuclear proteins. When vector pKRS-413, containing CAT driven by the mouse KRAS promoter, and KRAS quadruplex oligonucleotides were co-transfected in 293 cells, the expression of CAT was found to be downregulated to 40% of the control. On the basis of these data, we propose that the NHPPE of KRAS exists in equilibrium between a double-stranded form favouring transcription and a folded quadruplex form, which instead inhibits transcription. Such a mechanism, which is probably adopted by other growth-related genes, provides useful hints for the rational design of anticancer drugs against the KRAS oncogene.


Distribution of aromatase activity in the brain and peripheral tissues of passerine and nonpasserine avian species.
Many behavioral effects of testosterone on hypothalamic and limbic brain areas are mediated by the action, at the cellular level, of estrogens derived from local testosterone aromatization. Aromatase activity and cells containing the aromatase protein and mRNA have accordingly been identified in the brain areas involved in the control of behavior. The presence of an unusually high level of aromatase activity has been detected in the telencephalon of one songbird species, the zebra finch (Taeniopygia guttata), and it is suspected that this high telencephalic aromatase may be a specific feature of songbirds but this idea is supported only by few experimental data. The distribution of aromatase activity in the brain of zebra finches and of one nonsongbird species, the Japanese quail (Coturnix japonica), was compared with the distribution of aromatase activity in the brain of four species of free-living European songbirds, the chaffinch (Fringilla coelebs, Fringillidae), willow warbler (Phylloscopus trochilus, Sylviidae), great tit (Parus major, Paridae), and pied flycatcher (Ficedula hypoleuca, Muscicapidae). High levels of enzyme activity were observed in the diencephalon of all species. The high levels of aromatase activity that had been observed in the zebra finch telencephalon and were thought to be typical of songbirds were also present in the four wild oscine species but not in quail. None of these songbird species had, however, a telencephalic aromatase activity as high as that in the zebra finch, which may represent an extreme as far as the activity of this enzyme in the telencephalon is concerned. Measurable levels of aromatase activity were also detected in all songbird species in the liver and in the three other brain areas that were assayed, the optic lobes, cerebellum, and brain stem, with the exception of the cerebellum in willow warblers and quail, but no detectable activity was observed in the testes, muscle, and adrenals of all species. Additional studies will be needed to identify the functional significance of estrogen synthesis in areas that are not classically known to be implicated in the control of reproduction. Within a given species, the birds that had the highest plasma testosterone levels also displayed the highest levels of diencephalic aromatase activity and the interspecies differences in the two variables were positively related. This raises the possibility that the absolute level of diencephalic aromatase represents a species-specific characteristic under the control of plasma testosterone levels. There was, in contrast, no correlation between the aromatase activity in the telencephalon and the plasma testosterone levels but the enzyme activity was correlated with the plasma levels of luteinizing hormone. These data bring additional support to the idea that the diencephalic and telencephalic aromatases are controlled by independent mechanisms.


Protective effect of clusterin on oxidative stress-induced cell death of human corneal endothelial cells.
To investigate the protective effect of clusterin on oxidative stress-induced cell death of human corneal endothelial cells. Human corneal endothelial cells (HCECs) were cultured according to previously published methods. With treatment of various concentrations (0-50 mM) of tert-butyl hydroperoxide (tBHP) or clusterin, reactive oxygen species (ROS) producrion was measured using an oxidationsensitive fluorescent probe and 2'7'-dichlorofluorescin diacetate (DCFH-DA). Cell viability was assayed with a Cell Counting Kit-8. In HCECs, DCF-DA staining revealed that cells treated with a higher concentration of tBHP had higher fluorescent intensity than cells treated with clusterin, compared to control cells. Clusterin significantly inhibited tBHP-induced ROS production. Cell viability decreased with higher tBHP concentration. Cells treated with clusterin had higher viability than control cells at 5 mM tBHP. Clusterin effectively protected HCECs from ROS-induced cell death. Our data suggest that clusterin may protect HCECs from oxidative injury-mediated cell death via inhibition of ROS production.


Peak fat oxidation rate during walking in sedentary overweight men and women.
The aim of this study was to determine the relative exercise intensity that elicits maximal fat oxidation during walking in inactive and overweight men and women and evaluate any possible sex differences. Forty six healthy, sedentary, overweight men (age: 36.3 ± 1.3 years, body fat: 28.8 ± 0.8%, n = 28, mean ± SE) and women (age: 36.6 ± 1.8 years, body fat: 37.1 ± 0.8%, n = 18) participated in the study. Fat oxidation was calculated from expired air analysis using indirect calorimetry during an incremental treadmill walking test. Peak fat oxidation rate (PFO) was higher in men compared to women (0.31 ± 0.02 vs. 0.20 ± 0.02 g.min(-1); p < 0.001), but this difference disappeared when PFO was scaled per kg fat-free mass (4. 36 ± 0.23 vs. 3.99 ± 0.37 mg.kg fat free mass(-1).min(-1)). Also, the relative exercise intensity at which PFO occurred was similar for men and women and corresponded to 40.1 ± 1.8 and 39. 5 ± 2.3% of maximal oxygen uptake (VO2max) and 60.0 ± 1.4 and 57.8 ± 1.4% of maximal heart rate, respectively. The walking speed corresponding to PFO was 5.5 ± 0.2 and 5.0 ± 0.1 km·h(-1) for men and women, respectively. Regression analysis showed that sex, FFM and VO2max were significant predictors of PFO expressed in g.min(-1) (adjusted R(2) = 0.48, p = 0.01). However when PFO was scaled per kg FFM, only a small part of the variance was explained by VO2max (adjusted R(2) = 0.12, p < 0.05). In conclusion, peak fat oxidation rate and the corresponding relative exercise intensity were similar in male and female overweight and sedentary individuals, but lower compared to those reported for leaner and/or physically active persons. Walking at a moderate speed (5.0-5.5 km·h(-1)) may be used as a convenient way to exercise at an intensity eliciting peak fat oxidation in overweight individuals. Key pointsPeak fat oxidation rate scaled per kg fat-free mass and the corresponding relative exercise intensity are similar in male and female overweight and sedentary individuals, but lower compared to those reported for leaner and/or physically active persons.Walking at a moderate speed (5.0-5.5 km.h(-1)) may be used as a convenient way to exercise at an intensity eliciting peak fat oxidation in overweight individuals.The relationship between %HRmax and %VO2max in overweight individuals is different from that reported for normal-weight adults and should be taken into account to optimize exercise intensity using heart rate in obese individuals.Due to the low intensity corresponding to peak fat oxidation in overweight and sedentary persons and the inter-individual differences, exercise intensity for health benefits should be prescribed following individual testing.


Photo-tropotaxis based on projection through the cerebral commissure in the terrestrial slug Limax.
In the terrestrial slug, Limax, eyes are located at the tip of the superior tentacles. This animal has long been believed to show negative phototaxis through tropotaxis, i.e., it compares the two light intensities detected by bilateral eyes to move away from a light source. As one of the possible manifestations of such negative phototaxis, a circling movement has been observed: if one of the superior tentacles is removed, the slugs continuously move in the direction of the removed side. However, there has been no evidence demonstrating that this behavior is actually based on negative phototropotaxis. In this study, we showed that the slugs do not exhibit the circling behavior in the absence of light, and that amputation of the cerebral commissure also diminishes the circling behavior under light. We could detect light-evoked responses during electrical recording from the cut edge of the cerebral commissure. Labeling of the optic nerve with neurobiotin also revealed the presence of the commissural fibers that potentially transmit the light information to the contralateral cerebral ganglion. Our study suggests that the slug's circling behavior is based on phototropotaxis in which the light intensities detected by the bilateral eyes are compared through the cerebral commissure.


Epigenetic reprogramming of the zygote in mice and men: on your marks, get set, go!
Gametogenesis (spermatogenesis and oogenesis) is accompanied by the acquisition of gender-specific epigenetic marks, such as DNA methylation, histone modifications and regulation by small RNAs, to form highly differentiated, but transcriptionally silent cell-types in preparation for fertilisation. Upon fertilisation, extensive global epigenetic reprogramming takes place to remove the previously acquired epigenetic marks and produce totipotent zygotic states. It is the aim of this review to delineate the cellular and molecular events involved in maternal, paternal and zygotic epigenetic reprogramming from the time of gametogenesis, through fertilisation, to the initiation of zygotic genome activation for preimplantation embryonic development. Recent studies have begun to uncover the indispensable functions of epigenetic players during gametogenesis, fertilisation and preimplantation embryo development, and a more comprehensive understanding of these early events will be informative for increasing pregnancy success rates, adding particular value to assisted fertility programmes.


Synthesis and determination of absolute configuration of the bicyclic guanidine core of batzelladine A.
[reaction: see text] The synthesis of a selectively protected form of the bicyclic guanidine fragment of batzelladine A from L-aspartic acid is reported, thereby establishing the absolute configuration of the bicyclic guanidine ring system within the natural product.


[Benzodiazepines : known risks and recent data].
Benzodiazepines have been considered the treatment of choice for a variety of neuropsychiatric disorders. They are currently much more controversial and drugs considered less dangerous are generally preferred. This article summarizes the characteristics of the different benzodiazepines present on the Belgian market. It describes abuse and dependence, as well as the risks of these substances in specific populations or situations. New data suggest that there is a much higher risk of decease in case of a chronic use. Finally, recommendations on rational use and withdrawal are given.


Development of active tuberculosis in patients treated with biological disease-modifying antirheumatic drugs.
Biological disease-modifying antirheumatic drugs (bDMARDs) have been shown to be highly effective in the treatment of rheumatic conditions, but may increase the risk of infections. Development of tuberculosis (TB) while on bDMARD therapy is of particular concern in high TB burden settings such as Western Cape Province, South Africa. To describe the diagnosis, management and outcome of patients who developed active TB while receiving a bDMARD. Ten patients who screened negative for TB prior to initiation of a bDMARD subsequently developed active TB. TB was diagnosed between 10 months and 9 years from bDMARD initiation, suggesting new infection, and included 6 cases of extrapulmonary TB. All patients required multiple tests to confirm the diagnosis of TB, and all were successfully treated. TB can occur in patients on bDMARD therapy despite initial screening, and may have unusual, extrapulmonary manifestations that pose a diagnostic challenge.


Insights Into Microcirculation Underlying Critical Limb Ischemia by Single-Photon Emission Computed Tomography.
Perfusion difference is used as a parameter to evaluate microcirculation. This study aims to differentiate lower-limb perfusion insufficiency from neuropathy to prevent possible occurrence of failed back surgery syndrome (FBSS).Patients were retrospectively gathered from 134 FBSS cases diagnosed in the past 7 years. Up to 82 cases that were excluded from neuralgia by radiologic imaging, electrodiagnostic electromyography, and nerve conduction velocity were enrolled in this study. Perfusion difference was evaluated by single-photon emission computed tomography, and pain intensities were recorded via visual analog scale (VAS) score.Lower perfusion at the left leg comprises 51.2% (42 of 82) of the patients. The mean perfusion difference of the 82 patients was 0.86 ± 0.05 (range: 0.75-0.93). Patients with systemic vascular diseases exhibited significantly higher perfusion difference than that of patients without these related diseases (P < 0.05), except for renal insufficiency (P = 0.134). Significant correlation was observed between perfusion difference and VAS score (r = -0.78; P < 0.0001; n = 82).In this study, we presented perfusion difference as a parameter for evaluating microcirculation, which cannot be detected by ultrasonography or angiography.


The dewetting dynamics of the polymer thin film by solvent annealing.
The slippage effect of the polymer chains is investigated in the dewetting process of the polymer solution film. The solvent-induced dewetting is used in our experiments to study the dynamics of hole growth in the dewetting process of the polymer solution film. Our results show that in the case of the low molecular weight polystyrene (PS) film, the slippage effect of the polymer chains is not displayed and the radius of the holes is R approximately exp(t/tau); in the case of the higher molecular weight PS film, the slippage effect of the polymer chain is not valid in the case of the thin film and that is valid in the case of the thick film, and the dynamic process of hole growth divides into three stages (R approximately t, and then R approximately t(x) (23<x<1), finally, R approximately t). Besides, the solvent and substrate properties also influence the dewetting dynamics of the polymer solution film.


Triangles and crystals: on the geometry of qualitative research.
Triangulation has become increasingly appealing to researchers in nursing as a device to grasp the complexity of human phenomena, operationalize the holistic elan of nursing, and to accommodate both qualitative and quantitative approaches to inquiry. Yet, a misplaced ecumenicism, definitional drift, and conceptual misappropriation are evident in discussions of triangulation, which has become a technique for everything. Moreover, the triangle is somewhat lacking as image and metaphor for qualitative inquiry. As an idea and technique (in)formed by the triangle, triangulation should be used only to refer to a distinctive strategy for confirmation employed within research paradigms in which convergent and consensual validity are valued, and in which it is deemed appropriate to use information from one source to corroborate another.


Doing Good Again? A Multilevel Institutional Perspective on Corporate Environmental Responsibility and Philanthropic Strategy.
This study investigates the relationship between corporate environmental responsibility and corporate philanthropy. Using a sample of Chinese listed firms from 2008 to 2013, this paper examines the role of corporate environmental responsibility in corporate philanthropy and the moderating influence of the institutional environment using multilevel analysis. The results show that corporate eco-friendly events are positively associated with corporate philanthropic strategy to a significant degree. Provincial-level government intervention positively moderate the positive relationship between eco-friendly events and corporate philanthropy and government corruption is negatively moderate the relationship. All these results are robust according to robustness checks. These findings provide a new perspective on corporate philanthropic strategy as a means to obtain critical resources from the government in order to compensate for the loss made on environmental responsibility. Moreover, the institutional environment is proved here to play an important role in corporate philanthropic strategy.


Correlation of arterial and end-tidal carbon dioxide in spontaneously breathing patients during ambulatory gynecologic laparoscopy.
Laparoscopy can be performed while patients are under total intravenous anesthesia (TIVA), or sedated and breathing spontaneously through the normal airway. Respiratory monitoring is difficult when patients are sedated or anesthetized, however. The purposes of this study were to evaluate the reliability of end-tidal carbon dioxide (ETCO2) measurement for monitoring arterial carbon dioxide pressure (PaCO2), and to assess the PaCO2/ETCO2 gradient among patients receiving TIVA while breathing spontaneously through the normal airway. Sixty patients were divided into two groups: group 1 patients (n = 30) received general anesthesia with controlled ventilation, while group 2 patients (n = 30) received TIVA with spontaneous breathing through the normal airway; ETCO2 was sampled through a 10-French suction catheter inserted into the nasopharynx via the nasal airway. Arterial blood gas and ETCO2 were recorded at the time of preinduction, induction, CO2 insufflation, and change to Trendelenburg tilt position (20 degrees-30 degrees), and at 10-minute intervals thereafter. The results showed that ETCO2 was highly correlated with PaCO2 in group 1 (correlation coefficient r = 0.85), but not in group 2 (r = 0.55). In group 2, the PaCO2/ETCO2 gradient increased as time elapsed, with significant differences (p < 0.05) between the values at induction and those at 30 minutes after the change to the Trendelenburg position and thereafter. These results indicate that the ETCO2 and PaCO2 values correlate well during the first 20 minutes after the change to the Trendelenburg position in laparoscopy patients receiving TIVA with spontaneous breathing, but that PaCO2 monitoring is still necessary.


[Effect of a stabilization device for maintaining the balance of a CPR performer during ambulance transportation on quality of CPR in out-of-hospital cardiac arrest: a prospective randomized controlled trial].
To investigate the effect of a stabilization device for maintaining the balance of a cardiopulmonary resuscitation (CPR) performer during ambulance transportation on quality of CPR in out-of-hospital cardiac arrest (OHCA). A prospective randomized controlled trial was performed. 167 OHCA patients with cardiac arrest (CA) time < 10 minutes admitted to Cangzhou Central Hospital from October 2014 to January 2017 were enrolled, and divided into armed stabilization device group (n = 86) and unarmed stabilization device group (n = 81) by random number table. Restoration of spontaneous circulation (ROSC) rate, 24-hour survival rate and survival rate of discharge were evaluated. Compared with unarmed stabilization device group, ROSC rate (29.1% vs. 9.9%, χ2 = 9.691, P = 0.002), 24-hour survival rate (20.9% vs. 6.2%, χ2 = 7.649, P = 0.006) and survival rate of discharge (12.8% vs. 3.7%, χ2 = 4.485, P = 0.035) were significant increased in armed stabilization device group. CPR with stabilization device during ambulance transport could effectively ensure quality of CPR and improve prognosis in OHCA. Chinese Clinical Trial Registry, ChiCTR-IPR-14005337.


Interactions between Clostridium perfringens spores and Raw 264.7 macrophages.
Clostridium perfringens is the causative agent of a variety of histotoxic infections in humans and animals. Studies on the early events of C. perfringens infections have been largely focused on the interactions between their vegetative cells and macrophages. Consequently, in the current study we have examined the interactions between C. perfringens spores and Raw 264.7 macrophages. Raw 264.7 cells were able to interact and phagocytose Clostridium perfringens spores of a food poisoning isolate, strain SM101, and a non-food borne isolate, strain F4969, albeit to different extents. Phagocytosis and to a lesser extent, association, of C. perfringens spores by Raw 2647 macrophages was completely inhibited in presence of cytochalasin D. Complement increased association and phagocytosis of C. perfringens spores by Raw 264.7 macrophages. Survival of C. perfringens spores during macrophage infection seems to depend on the ability of spore germination during infection as: (i) F4969 spores germinated during infection with Raw 264.7 macrophages and subsequently killed by macrophages; and (ii) SM101 spores remained dormant inside Raw 264.7 macrophages and thus survived up to 24 h of infection. The in vitro spore-resistance factors, α/β-type SASP, SpmA/B proteins and spore's core water content, seems to play no role in mediating SM101 spore-resistance to macrophages. Collectively, these results might well have implications in understanding the initial stages of infections by C. perfringens spores.


Comparative Pore Structure Analysis of Dextran-Coated Polystyrene Particles.
Porous poly(styrene-divinylbenzene) (PS-DVB) particles were modified by adsorption of hydrophobically-modified dextrans, to provide chromatographic matrices for biomolecule chromatography. The dextran distribution and the pore characteristics of various coated PS-DVB beads were examined using nitrogen adsorption-desorption, mercury intrusion, and size exclusion chromatography. It was found that the adsorption of dextran does not result in homogeneous layers but rather in inhomogeneous ones. At high dextran loading and high content of hydrophobic groups in the adsorbed polymer, most of the pores of the macroporous rigid material are filled with a soft and porous dextran network being stabilized by hydrophobic interactions. According to chromatographic experiments, most of the surface was nevertheless expected to be covered at least by a thin and dense protecting layer since proteins-even those that are small enough to penetrate the dextran network-cannot interact nonspecifically with the internal pore surface. At low content of hydrophobic groups, dextran deposits preferentially as a thicker and more diffuse layer. However, the thickness of the coating is expected to be irregular and probably contributes to an increase in the roughness of the polystyrene surface. Copyright 1999 Academic Press.


The Controversial History of Hormone Replacement Therapy.
The history of hormone replacement therapy (HRT) started in the 1960s, with very high popularity in the 1990s. The first clinical trials on HRT and chronic postmenopausal conditions were started in the USA in the late 1990s. After the announcement of the first results of the Women's Health Initiative (WHI) in 2002, which showed that HRT had more detrimental than beneficial effects, HRT use dropped. The negative results of the study received wide publicity, creating panic among some users and new guidance for doctors on prescribing HRT. The clear message from the media was that HRT had more risks than benefits for all women. In the following years, a reanalysis of the WHI trial was performed, and new studies showed that the use of HRT in younger women or in early postmenopausal women had a beneficial effect on the cardiovascular system, reducing coronary disease and all-cause mortality. Notwithstanding this, the public opinion on HRT has not changed yet, leading to important negative consequences for women's health and quality of life.


Effectiveness and failure rate of the varicella vaccine in an outbreak in Jiangsu, China: a 1:2 matched case-control study.
Background: The varicella vaccine is not included in the national childhood immunization schedules in China, although one-dose varicella vaccine has been suggested for susceptible children aged 1-12 years in Jiangsu Province. However, varicella epidemics and outbreaks are frequently reported. We investigated a varicella outbreak in an elementary school to explore the risk factors for varicella transmission and vaccine failure.Methods: A 1:2 matched case-control study was carried out. Participant data were collected with standardized questionnaires. For each case, we enrolled two controls: a subject with high exposure in the same classroom as the case and a subject with low exposure in a different classroom. Data regarding vaccination status and medical and exposure histories were analyzed.Results: Fifty-one cases were reported during the outbreak; 26 cases (51%) were breakthrough varicella. Varicella vaccine immunization history (P < .001, OR = 0.19, 95% CI = 0.08-0.45) and the presence of siblings (P = .037, OR = 0.45, 95% CI = 0.21-0.95) were protective factors in preventing varicella infection. Contact with varicella patients increased the risk of varicella infection (P = .028, OR = 3.39, 95% CI = 1.14-10.09). Breakthrough varicella cases tended to present a milder rash (P = .049), fewer complications (P = .02), fewer rash sites (P = .02) and a shorter duration of active lesions (P = .001). One pneumonia case and one encephalitis case were reported in breakthrough cases. Age <15 months at the time of vaccination increased the risk of breakthrough varicella (P = .012). The adjusted vaccine effectiveness was 81%.Conclusions: One-dose varicella vaccine is effective at alleviating clinical manifestations. The moderate coverage provided by one dose cannot prevent varicella outbreaks, and vaccination after 15 months of age should be considered in the immunization schedule; a two-dose strategy is highly recommended.


Antiepileptic Drugs for Preventing Seizures in Patients with Chronic Subdural Hematoma.
Chronic subdural hematoma (CSH) is an accumulation of blood within the intracranial subdural space. It is associated with minor traumatic events and affects mostly the elderly. CSH can be effectively treated surgically with good outcomes, although the recurrence rate is high. Epileptic seizures are one of the major complications associated with CSH, either in the pre or postoperative period. The incidence rate of new onset seizures after CSH diagnosis ranges between 3% and 23%. However, the benefit of using prophylactic antiepileptic drugs in these patients is controversial with significant variations in clinical practice. It ranges from routine to total absence of use in this clinical context. The best current evidence does not allow any firm conclusion on whether such prophylactic treatment is effective, that is if it prevents the development of epileptic seizures. Furthermore, these drugs are associated with important adverse events. A systematic literature review found no controlled randomized trials evaluating the risk/benefit of the prophylactic use of anticonvulsants for people with CSH and retrospective studies showing contradictory results. Moreover, these observational studies are outdated and do not evaluate new generation drugs. Herein, we discuss the evidence for the use of antiepileptic drugs for preventing seizures in patients with CSH, with a particular focus on the subgroup of people most likely to benefit (such as the elderly and alcohol abusers), as well as the possible safety advantages of the new antiepileptic drugs.


Current Use and Future Considerations for Concussion Telemedicine Healthcare in Canada.
To examine the use of telemedicine among Canadian concussion providers and clinics before and after the COVID-19 pandemic onset and identify barriers and facilitators for future use. Ninety-nine concussion clinics and healthcare providers across Canada that offered one or more clinical concussion-related service were identified using standardized online searches and approached to complete a cross-sectional online survey. Thirty clinics or providers completed the survey and two completed subsections of the survey (response rate of 32.3%). Only 28.1% of respondents indicated that they used telemedicine to provide care prior to the COVID-19 pandemic. Providers most commonly using telemedicine prior to the pandemic were occupational therapists and physicians, while the most commonly used services were in-person videoconferencing and eConsultation. Most respondents (87%) indicated their clinic's use of telemedicine changed following the onset of the COVID-19 pandemic including new use of in-person video-conferencing, telephone calls, and eConsultation. Ninety-three percent indicated that they would consider using telemedicine to provide care to their concussion patients once the pandemic was over. Barriers needed to be overcome to facilitate use or greater use of telemedicine-based services were the inability to conduct a complete physical examination, lack of appropriate reimbursement, lack of start-up, and maintenance funding and medico-legal risk. Telemedicine was used by a minority of Canadian concussion clinics and providers prior to the COVID-19 pandemic but was rapidly adopted by many facilities. This study provides important insight into the factors that must be considered to optimize use of telemedicine in concussion care in the future.


Detection and quantification of 1,N(6)-ethenoadenine in human placental DNA by mass spectrometry.
Exocyclic DNA adducts have been reported to derive from various exogenous as well as endogenous sources, such as lipid peroxidation. Among them, 1,N(6)-ethenoadenine (epsilonAde) has previously been detected in tissue DNA of untreated rodents and humans by an immunoaffinity/(32)P-postlabeling method. This study reports detection and quantification of the endogenous epsilonAde adduct in the same human placental DNA by three independent assays, namely, GC/MS, LC/MS, and HPLC/fluorescence. Using a recently reported gas chromatography/negative ion chemical ionization/mass spectrometry (GC/NICI/MS) method [Chen, H.-J. C., et al. (1998) Chem. Res. Toxicol. 11, 1474], the level of epsilonAde in human placental DNA from a commercial source was found to be 2.3 adducts per 10(6) Ade bases. To confirm these findings, a liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI/MS/MS) method was developed for epsilondAdo. With this LC/MS assay, epsilondAdo was detected at the level of 2.5 adducts per 10(6) dAdo nucleosides in the same human placental DNA. The stable isotopes of epsilonAde and epsilondAdo were added as internal standards in both GC/MS and LC/ESI/MS/MS assays, respectively, and thus provided high specificity, reproducibility, and accurate quantification. The relatively high levels of epsilonAde in this human placental DNA detected by mass spectrometry were further verified by HPLC/fluorescence analysis. The GC/MS method was validated by the HPLC/fluorescence assay using calf thymus DNA treated with chloroacetaldehyde or by the LC/MS method with 2, 3-epoxy-4-hydroxynonanal-modified calf thymus DNA. The epsilonAde level in human placental DNA freshly isolated in the presence of an antioxidant was similar to that in DNA from the commercial source. Since epsilonAde is a potential mutagenic lesion, analysis of epsilonAde by the specific and sensitive GC/NICI/MS method may provide a useful biomarker in cancer risk assessment.


Current progress in xenogeneic tolerance.
The present review updates the current status of research regarding the immunologic responses of the recipient following xenotransplantation. Additionally, we present the recent progress with attempts to induce xenogeneic tolerance induction. There continues to be great interest in xenotransplantation. Recently, descriptions of the mechanisms responsible for attempted T-cell xenogeneic tolerance in both large and small animal models have improved xenogeneic graft survivals. Additionally, the cellular signaling mechanisms, such as those involving CD39, CD44, and CD47, are proving to be highly important. Using the mixed chimerism approach to tolerance in xenogeneic model may be encouraging, especially given the recent clarification of the role for macrophage-induced phagocytosis of xenogeneic donor cells. Induction of tolerance to xenogeneic antigens has been accomplished only in small animals; however, graft survivals in large animal models continue to improve. Further clarification of both the adaptive and innate immune responses to xenogeneic antigens is required for success to continue.


Molecular cloning, mRNA expression and chromosomal localization of mouse angiotensin-converting enzyme-related carboxypeptidase (mACE2).
We isolated two mouse cDNA clones which show significant similarities with human angiotensin-converting enzyme-related carboxypeptidase (ACE2). The cDNAs were 2746 and 1995 bp in length and seemed to arise from the same gene by alternative splicing. The longer cDNA encoded a 798-amino acid protein containing the sequence motif conserved among zinc metallopeptidases. Mouse ACE2 showed 83% identity with human ACE2. Northern blot analysis revealed that 2.8- and 2.0-kb transcripts were expressed mainly in the kidney and the lungs. The mouse ACE2 gene was mapped to chromosome X 70.5 cM.


Use and perceptions of the internet for sexual information and partners: a study of young men who have sex with men.
The Internet has opened many doors with its accessibility to information, entertainment and web-based communities. For young men who have sex with men (YMSM), the Internet can provide access to information on relevant sexual behavior and health information, stories from other men about relationship issues, and a venue for locating potential sexual and dating partners. Understanding YMSM's motivations for going online for information, advice or sexual relationships, is important as the Internet becomes increasingly used not only as a space to find sexual partners, but also as a venue for HIV and STI interventions. Having an understanding of the risks associated with searching for partners online, and how and why YMSM use the Internet for a variety of purposes, can inform the development of more effective Internet-based risk reduction programs. This article presents qualitative and quantitative data from the Healthy Young Men's Study, a longitudinal study of an ethnically diverse cohort of 526 YMSM. Qualitative interviews (N = 24) described not only the prevalence of using the Internet for finding sexual partners and the possible benefits and risks associated with that practice, but also the processes and perceptions of using this mechanism. Our data indicate that YMSM used the Internet to find information related to sex and sexuality, seek friendships, sexual partners as well as "hook-ups" or casual sex. Findings were presented in relation to how YMSM researchers and interventionists can identify how to most effectively reach YMSM through online methods.


Transcriptional Changes in nAChRs, Interactive Proteins and P450s in Locusta migratoria manilensis (Orthoptera: Acrididae) CNS in Response to High and Low Oral Doses of Imidacloprid.
The insect central nervous system (CNS) is the target for many insecticides, and changes in transcript levels could be expected after insecticide applications. In this study, differentially expressed genes in the locust (Locusta migratoria manilensis) CNS in response to imidacloprid treatments at low dose (LD, 10% mortality) and high dose (HD, 80% mortality) were identified. Two nicotine acetylcholine receptor (nAChR) subunits genes and 18 interacting protein genes were regulated at LD, and only one nAChR subunit gene and 11 interacting proteins were regulated at HD. Among the 110 annotated P450 unigenes, 43 unigenes were regulated at LD and 34 unigenes were regulated at HD. Most of the differentially expressed P450 unigenes were mapped to CYP4, in which most unigenes were upregulated at LD, but downregulated at HD. Totally, the numbers and regulation levels of the regulated genes were more at LD than that at HD. Seventeen unigenes were selected to test their expression changes following insecticide treatments by qRT-PCR, in which the changes in more than half of the selected genes were verified. The results revealed the variation in the response of locusts to different insecticide pressure, such as different doses.


A study of the dicyclohexylcarbodiimide-binding component of the mitochondrial ATPase complex from beef heart.
1. The binding of [14C]-dicyclohexylcarbodiimide to membrane proteins of beef heart mitochondria has been investigated using dodecylsulphate/polyacrylamide gel electrophoresis. Upon incubation of submitochondrial particles with low concentrations of dicyclohexylcarbodiimide (5 nmol/mg protein) radioactivity was incorporated into three components with apparent molecular weights of 30000, 18000 and less than 6500. Only the two smaller components were found to be extracted into chloroform/methanol. The same two components were labelled when the isolated ATPase complex or a reconstituted F0F1 system was incubated with low concentrations of dicyclohexylcarbodiimide. High concentrations of dicyclohexylcarbodiimide (20-100 nmol/mg protein) resulted in binding to several mitochondrial proteins. 2. The maximal amount of dicyclohexylcarbodiimide which can bind to submitochondrial particles, the isolated ATPase complex, and the reconstituted F0F1 system was found to exceed the amount required for maximal inhibition of the ATPase activity by several-fold. The distribution of the bound [14C]dicyclohexylcarbodiimide between the different dicyclohexylcarbodiimide-binding components was investigated as a function of dicyclohexylcarbodiimide concentration. The smallest and largest components revealed a high affinity for dicyclohexylcarbodiimide-binding which paralleled the inhibition of ATPase activity. The intermediate component had a markedly lower affinity for dicyclohexylcarbodiimide-binding. 3. The larger dicyclohexylcarbodiimide-binding component of the isolated ATPase complex can be converted into the smaller component by treatment of the ATPase complex with performic acid. Partial conversion can also be achieved by extraction of the band from the dodecylsulphate-polyacrylamide gel after electrophoresis, followed by re-electrophoresis. The observations suggest that the larger component may be an oligomer of the smaller one. 4. Using concentrations of oligomycin and dicyclohexylcarbodiimide which were equal to or greater than those required for maximal inhibition of the ATPase activity, oligomycin was found to diminish the binding of [14C]dicyclohexylcarbodiimide to both dicyclohexylcarbodiimide-binding components of the isolated ATPase complex.


[Characteristics of the Gypsy population].
"The study sums up the number and socio-economic characteristics of [the] gipsy population in Hungary. The history of gipsy surveys, dating back more than one hundred years, is reviewed.... The present situation is described drawing on the 1990 population census and the data of a special gipsy survey carried out in 1993. In the course of their analysis the authors discuss in detail the demographic characteristics, regional structure, labour market position, household budget situation, and housing conditions of gipsies." (SUMMARY IN ENG)


RGD peptides immobilized on a mechanically deformable surface promote osteoblast differentiation.
The major objective of this work was to attach bone cells to a deformable surface for the effective transmission of force. We functionalized a silastic membrane and treated it with 3-aminopropyltriethoxysilane (APTS). A minimal RGD peptide was then covalently linked to the aminated surface. MC3T3-E1 osteoblast-like cells were cultured on the arginine-glycine-aspartic acid (RGD)-treated membrane for 3-15 days and cell attachment and proliferation was evaluated. We observed that cells were immediately bound to the membrane and proliferated. After 8 days on the material surface, osteoblasts exhibited high levels of ALP staining, indicating that the cells were undergoing maturation. Alizarin red staining and Fourier transform infrared (FTIR) analysis showed that the mineral formed by the cells was a biological apatite. The second objective was to apply a mechanical force to cells cultured on the modified silicone membrane. Dynamic equibiaxial strain, 2% magnitude, and a 0.25-Hz frequency were applied to bone cells for 2 h. Osteoblasts elicited increased phalloidin fluorescence, suggesting that there was reorganization of the cytoskeleton. Furthermore, the applied strain elicited increased expression of the alpha(v)beta3 integrin receptor. We concluded that the covalent binding of RGD peptides to a silicone membrane provides a compatible surface for the attachment and subsequent differentiation of osteoblasts. Moreover, the engineered surface transduces applied mechanical forces directly to the adherent cells via integrin receptors.


Near-infrared (808 and 980 nm) excited photoluminescence study in Nd-doped Y2O3 phosphor for bio-imaging.
The upconversion (UC) process in lanthanide-doped nanophosphors has attracted great research interest for its extensive application potential in biological in vitro and in vivo imaging due to the high tissue penetration depth of near-infrared excitation and low autofluorescence background. In this article, the authors report the synthesis of oxide nanophosphor of size ⩽50 nm, which forms stable aqueous dispersion. The photoluminescence study is made on the nanophosphor upon 808 and 980 nm diode laser excitations. The 808 nm excitation resulted in strong emission at 795 nm due to the 4K13/2 → 4I13/2 transition along with other emissions from the Nd3+ ion. The 980 nm excitation has resulted in it turning green in the 525-560 nm range and is assigned to the 4S3/2 → 4I15/2 transition of the Er3+ ion, which is supposed to be present in a trace amount in the sample. The observation of strong UC emission indicates that the sample can be used for UC-based bio-imaging applications.


PgLOX6 encoding a lipoxygenase contributes to jasmonic acid biosynthesis and ginsenoside production in Panax ginseng.
Ginsenosides, the valuable pharmaceutical compounds in Panax ginseng, are triterpene saponins that occur mainly in ginseng plants. It was shown that in vitro treatment with the phytohormone jasmonic acid (JA) is able to increase ginsenoside production in ginseng plants. To understand the molecular link between JA biosynthesis and ginsenoside biosynthesis, we identified a JA biosynthetic 13-lipoxygenase gene (PgLOX6) in P. ginseng that promotes ginsenoside production. The expression of PgLOX6 was high in vascular bundles, which corresponds with expression of ginsenoside biosynthetic genes. Consistent with the role of PgLOX6 in synthesizing JA and promoting ginsenoside synthesis, transgenic plants overexpressing PgLOX6 in Arabidopsis had increased amounts of JA and methyl jasmonate (MJ), increased expression of triterpene biosynthetic genes such as squalene synthase (AtSS1) and squalene epoxidase (AtSE1), and increased squalene content. Moreover, transgenic ginseng roots overexpressing PgLOX6 had around 1.4-fold increased ginsenoside content and upregulation of ginsenoside biosynthesis-related genes including PgSS1, PgSE1, and dammarenediol synthase (PgDDS), which is similar to that of treatment with MJ. However, MJ treatment of transgenic ginseng significantly enhanced JA and MJ, associated with a 2.8-fold increase of ginsenoside content compared with the non-treated, non-transgenic control plant, which was 1.4 times higher than the MJ treatment effect on non-transgenic plants. These results demonstrate that PgLOX6 is responsible for the biosynthesis of JA and promotion of the production of triterpenoid saponin through up-regulating the expression of ginsenoside biosynthetic genes. This work provides insight into the role of JA in biosynthesizing secondary metabolites and provides a molecular tool for increasing ginsenoside production.


Carney complex.
Carney complex is a rare, dominantly inherited multiple endocrine neoplasia syndrome, affecting endocrine glands as the adrenal cortex (causing Cushing's syndrome), the pituitary and the thyroid. It is associated with many other nonendocrine tumors, including cardiac myxomas, testicular tumors, melanotic schwannoma, breast myxomatosis, and abnormal pigmentation (lentiginosis) or myxomas of the skin. The gene located on the CNC1 locus was identified 12 years ago as the regulatory subunit 1A (R1A) of the protein kinase A (PRKAR1A) located at 17q22-24. Inactivating heterozygous germline mutations of PRKAR1A are observed in about two thirds of Carney complex patients with some genotype-phenotype correlation useful for follow-up and prognosis. More rarely, mutations of phosphodiesterase genes have been reported in patients presenting mainly with Cushing's syndrome. In vitro and in vivo studies help to understand how R1A inactivation leads to tumorigenesis. PRKAR1A appears to be a relatively weak tumorigenic signal which can cooperate with other signaling pathways and tumor suppressors.


Scaffold-Free Fabrication of Osteoinductive Cellular Constructs Using Mouse Gingiva-Derived Induced Pluripotent Stem Cells.
Three-dimensional (3D) cell constructs are expected to provide osteoinductive materials to develop cell-based therapies for bone regeneration. The proliferation and spontaneous aggregation capability of induced pluripotent stem cells (iPSCs) thus prompted us to fabricate a scaffold-free iPSC construct as a transplantation vehicle. Embryoid bodies of mouse gingival fibroblast-derived iPSCs (GF-iPSCs) were seeded in a cell chamber with a round-bottom well made of a thermoresponsive hydrogel. Collected ball-like cell constructs were cultured in osteogenic induction medium for 30 days with gentle shaking, resulting in significant upregulation of osteogenic marker genes. The constructs consisted of an inner region of unstructured cell mass and an outer osseous tissue region that was surrounded by osteoblast progenitor-like cells. The outer osseous tissue was robustly calcified with elemental calcium and phosphorous as well as hydroxyapatite. Subcutaneous transplantation of the GF-iPSC constructs into immunodeficient mice contributed to extensive ectopic bone formation surrounded by teratoma tissue. These results suggest that mouse GF-iPSCs could facilitate the fabrication of osteoinductive scaffold-free 3D cell constructs, in which the calcified regions and surrounding osteoblasts may function as scaffolds and drivers of osteoinduction, respectively. With incorporation of technologies to inhibit teratoma formation, this system could provide a promising strategy for bone regenerative therapies.


Receptor mapping in neuropharmacology by autoradiography: some technical problems.
In the past decade, substantial advances in receptor mapping have been made. It is now as feasible to carry out receptor localizations as it is to carry out neurotransmitter localizations. A great deal of data has accumulated on various technical procedures and it is clear that significant problems occur with tritiated ligands. These problems involve different autoradiographic efficiencies in tissue regions, and steps must be taken to either correct for these different efficiencies or to eliminate them. It seems that I125-labeled ligands will become more and more important in the field.


[Study on the chemical components of Gardenia jasminoides].
To investigate the chemical components of Gardenia jasminoides. Various column chromatography were used in the isolation and purification. Physiochemical constant determination and spectral analysis were adopted to determine the chemical structures. Ten compounds were isolated and elucidated as syringic acid (1), syringaldehyde (2), vanillic acid (3), 3-hydroxy-vanillic acid (4), 3, 4, 5-trimethoxy-phenol (5), 4-hydroxy-3,5-dimethoxy-phenol (6), 4-methoxy-benzaldehyde (7), 7-hydroxy-5-methoxy-chromone (8), crocin-1 (9), crocin-2 (10). Compounds 2, 4 - 8 are first isolated from this plant.


Birthweight-specific infant mortality risks for Native Americans and whites, United States, 1960 and 1984.
We used NCHS natality and linked-birth/death certificate tapes to compare birthweight-specific neonatal and postneonatal mortality risks for Native Americans and whites in 1960 and in 1984. The birthweight distributions for the two groups were similar both years. Native American neonatal mortality risk dropped from 20.2 in 1960 to 5.2 in 1984, and the relative risk for Native Americans with respect to whites fell from 1.31 in 1960 to a nonsignificant difference in 1984. Postneonatal mortality risks for Native Americans fell from 27.5 in 1960 to 6.2 in 1984, with a drop in the relative risk from 5.2 to 2.1. Although the relative improvements for Native Americans were highest in postneonatal survival, Native Americans still had over twice the level of white postneonatal mortality. Birthweight was positively associated with survival for both groups, but the odds of Native American neonatal death were affected less by low and very low birthweights. For both groups, improvements in neonatal mortality were highest at the lower birthweights, while the gains in postneonatal survival benefitted normal and high birthweight infants most.


CD8 and CD4 T Cell Populations in Human Kidneys.
At border sites, and in internal organs, tissue resident memory T cells (TRM) contribute to the immune barrier against pathogens like viruses, bacteria, fungi, and cancer. However, information on the presence and function of these cells in the human kidney is scant. In order to better understand the T cell-mediated immunological defense in this organ, we aimed to determine phenotypic and functional aspects of CD8 and CD4 T cells present in healthy and allograft kidney tissue. Using multichannel flow cytometry, we assessed the phenotype and function of T cells in healthy renal tissue samples (n = 5) and kidney allograft tissue (n = 7) and compared these aspects to T cells in peripheral blood from healthy controls (n = 13). Kidney tissue samples contained substantial amounts of CD8 and CD4 T cells. In contrast to the circulating cells, kidney T cells frequently expressed CD69 and CD103, and were more often actively cycling. Furthermore, nearly all kidney T cells expressed CXCR3, and often expressed CXCR6 compared to T cells in the circulation. Markedly, kidney T cells produced greater quantities of IFNγ than circulating cells and were frequently polyfunctional. Functional T cells with the characteristic traits of TRM reside in human kidney tissues. These cells are more often actively cycling and frequently express CXCR3 and CXCR6.


Kidney protection in preventing post-ischaemic renal failure during thoracoabdominal aortic aneurysm repair: does prostaglandin E1 together with cooling provide more protection than cooling alone?
Prostaglandin E1 (PGE1) is known to have a positive effect on kidney function after kidney ischaemia due to aortic clamping. Side effects of PGE1 are a decrease of systemic blood pressure and prevention of thrombocyte clotting, both being undesired during repair of thoracoabdominal aortic aneurysms (TAA). The aim of this study was to evaluate, whether intraoperative and intraarterial kidney perfusion with 4 degrees Ringer's lactate plus 1000 IU of heparin/l plus 20 micrograms PGE1/l is more effective in preventing postischaemic kidney dysfunction than cold perfusion without PGE1. In the time period from I/1996 until X/1998 58 patients underwent aortic repair for TAA type II, III, or IV (Crawford's classification). Ten patients fulfilled the criteria for this study: renal artery stenosis or occlusion was excluded by angiography pre- and postoperatively. By means of szintigraphy an at least 30% participation in renal function had to be proven for every kidney. Intraoperatively both kidneys had to be excluded from circulation simultaneously. The left kidney in each patient was perfused with 4 degrees Ringer's lactate plus 1000 IU of heparin/l plus 20 micrograms PGE1/l. The right kidney was perfused with a solution of the same temperature plus heparin but without PGE1. There was an intermittent increase of creatinin and/or urea in each patient postoperatively. By renal szintigraphy, which was performed after a mean time of 9 (5-13) days postoperatively, a shift of renal function from one kidney to the other could be excluded. In this experimental setting no additional benefit for kidney function could be detected, when under conditions of ischaemia kidneys were perfused with 4 degrees Ringer's lactate plus 1000 IU of heparin/l plus 20 micrograms PGE1/l compared to kidneys perfused with the same solution without PGE1.


Autism in a child with common variable immunodeficiency.
Autism is a neurodevelopmental disorder, characterized by poor social interaction and communication impairment and repetitive behavior. Autism is considered as a genetic and multifactorial disorder, with diverse risk factors involved.Herein, we report a 13-year-old male with common variable immunodeficiency (CVID), who was diagnosed with autism at the age of 3 years old. As there are some evidences about the role of the immune system defects in the pathogenesis of autism, specific primary antibody deficiency diseases such as CVID might predispose some affected cases to such neurodevelopmental disorders.


Discovery of Novel 3-Cyanopyridines as Survivin Modulators and Apoptosis Inducers.
The overexpression of survivin is usually accompanied by an increased resistance of cancer cells to chemotherapeutic agents in addition to cancer aggressiveness. Consequently, survivin is considered as an attractive target to develop new promising anticancer candidates. A series of novel 3-cyanopyridine derivatives was synthesized and assessed for their cytotoxic activity against three human cancer cell lines: prostate carcinoma (PC-3), breast cancer (MDA-MB-231) and hepatocellular carcinoma (HepG2). In addition, their activities were evaluated in comparison with a standard anticancer drug 5-FU. Compounds 5c and 5e both exhibited promising cytotoxicity against all the tested cell lines; especially, 5e showed better cytotoxic effect than the reference drug 5-FU. In order to evaluate the safety of these compounds, they were tested on the normal cell line WI-38, revealing their toxic selectivity toward cancer cells over normal ones. Further studies were performed in order to understand their mechanism of action; we examined the ability of our promising compounds 5c and 5e to induce cell cycle arrest. Both resulted in a notable induction of cell cycle arrest at the G2/M phase, along with an increase in the DNA content in the pre-G1 phase, giving us an indication of the incidence of apoptosis. 5c and 5e were further subjected to additional study using Annexin V-FITC assay in order to evaluate their ability to induce apoptosis. The results showed a marked increase in the early and late apoptotic cells, as well as an increase in the percentage of necrosis. Furthermore, Western blotting assay was accomplished using different concentrations of 5c and 5e. The results revealed a striking reduction in survivin expression through proteasome-dependent survivin degradation in addition to a decrease in the expression of some other inhibitor of apoptosis proteins (IAP) family proteins: Livin, XIAP, and C-IAP1 in a concentration-dependent manner. A docking study of 5c and 5e compounds in the dimerization site of survivin was also performed, showing agreement with the in vitro anti-survivin activity.


[Effect of Acorus tatarinowii Schott on the amino acid neurotransmitters in the striatum focal cerebral ischemia in rat].
To research the change of concentration of the amino acid neurotransmitters in the striatum focal cerebral ischemia in rat and the effect of Acorus tatarinowii Schott, one of inducing resuscitation drugs, for 4 of amino acid neurotransmitters. Twenty four rats were divided into four groups (n = 6): control group, cerebral ischemia group, sham operation group and Acorns tatarinowii Schott treated group. Rats were established into models of cerebral ischemia by occluding bilateral thread cork method. Formation sampling were performed in a striatum area using microdialysis and the detection of biological sample including aspartic acid, glutamic acid, glycine and gamma-aminobutyric acid by high performance liquid chromatography (HPLC) electrochemical detector system. Compared with the control, the all contents of 4 kinds of the amino acids were significantly increased during cerebral ischemia (P < 0.01). Compared with the cerebral ischemia group, the contents of aspartic acid, glutamic acid that were excitatory amino acids were remarkably decreased in the striatum for Acorus tatarinowii Schott treated group (P < 0.01), It was no significant influence on gamma-aminobutyric acid and glycine that belonged to inhibitory amino acid in a nascent condition but with a elevating in the later period of microdialysis. Acorus tatarinowii Schott can enter the cerebral parenchyma through blood brain barrier and cut down glutamic acid,aspartic acid increased during cerebral ischemia. As a result, the neurotoxicity attributed to the excitatory amino acid has been released in excessive amounts declined so as to avoid the secondary impairment of neurons caused by excitatory amino acids pernicious effects after ischemia. It may be one of the protective mechanism of drugs for inducing resuscitation resembling EAA receptor antagonists to ischemi brain.


The association between nutrition and behavioural health in a US Army population.
The relationship between nutrition and behavioural health (BH) outcomes has been established in the literature. However, the relationship between nutrition and anxiety is unclear. Furthermore, the relationship between nutrition and BH outcomes has not been examined in a US Army Soldier population. This study sought to understand the relationship between Soldiers' nutritional intake and anxiety as well as depression. This cross-sectional study utilised multivariable logistic regression analyses to examine the relationship between nutritional intake and BH outcomes. The study utilised data collected in 2018 during a BH epidemiological consultation conducted at one Army installation. Participants were 7043 US Army Soldiers at one Army installation. Of the Soldiers completing the survey, 12 % (n 812) screened positive for anxiety and 11 % (n 774) for depression. The adjusted odds of anxiety were significantly higher among Soldiers who reported low fruit intake compared with Soldiers who reported high fruit intake (adjusted OR (AOR) 1·36; 95 % CI 1·04, 1·79). The adjusted odds of depression were higher for Soldiers who reported low fruit intake (AOR 1·35; 95 % CI 1·01, 1·79) and/or low green vegetable intake (AOR 1·37; 95 % CI 1·02, 1·83). Lastly, the adjusted odds of depression were lower for Soldiers who reported low sugary drink intake (AOR 0·62; 95 % CI 0·48, 0·81). This study is the first to examine the important connection between nutritional intake and anxiety and depression at a US military installation. The information learned from this study has implications for enhancing Soldiers' nutritional knowledge and BH, ultimately improving Soldiers' health and medical readiness.


Mutations that confer resistance to template-analog inhibitors of human immunodeficiency virus (HIV) type 1 reverse transcriptase lead to severe defects in HIV replication.
We isolated two template analog reverse transcriptase (RT) inhibitor-resistant mutants of human immunodeficiency virus (HIV) type 1 RT by using the DNA aptamer, RT1t49. The mutations associated, N255D or N265D, displayed low-level resistance to RT1t49, while high-level resistance could be observed when both mutations were present (Dbl). Molecular clones of HIV that contained the mutations produced replication-defective virions. All three RT mutants displayed severe processivity defects. Thus, while biochemical resistance to the DNA aptamer RT1t49 can be generated in vitro via multiple mutations, the overlap between the aptamer- and template-primer-binding pockets favors mutations that also affect the RT-template-primer interaction. Therefore, viruses with such mutations are replication defective. Potent inhibition and a built-in mechanism to render aptamer-resistant viruses replication defective make this an attractive class of inhibitors.


Perceptions of patients and healthcare providers on patient education to improve oral anticoagulant management.
Education of patients is thought to be key to high-quality oral anticoagulant (OAC) medication management. Theoretically, improving patients' knowledge should improve their self-management skills and adherence. The study's objective was to explore the opinions of healthcare providers and patients on the desired content and format of patient education on OACs, in addition to perceived barriers to high-quality patient education. We applied qualitative descriptive methods in a focus group study on OAC management. Five focus group discussions were conducted in two health regions in Southwestern Ontario from 2017 to 2018 with 19 patients, 7 caregivers and 16 healthcare providers (physicians, nurses and pharmacists). During the focus groups, participants discussed their experiences with OAC education and made suggestions about the content and format for patient education on OACs. Transcripts were analysed using conventional content analysis. We identified the five themes of patient education on OAC management: content of OAC education (rationale, risk and appropriate drug administration methods), the best times for providing OAC education (time of OACs initiation along with continuing education), preferred education delivery strategies (case management targeted patient information summaries from authoritative sources such as Thrombosis Canada and video education), patient and community pharmacist engagement in OAC education, and perceived barriers to optimal patient education (patients depending too much on their healthcare providers for advice, the limited time patients spend with healthcare providers, gaps in clear communication between providers and the lack of a nationally or provincially coordinated OAC management programme). Our findings suggest that patients, caregivers and healthcare providers support the need for education on OACs, including for patients taking DOACs. Specific important content and proper education format are needed. The optimal combination of content, format, duration, timing and sources for OAC education requires further research.


Niraparib in ovarian cancer: results to date and clinical potential.
Ovarian cancer is the first cause of death from gynaecological malignancy. Germline mutation in BRCA1 and 2, two genes involved in the mechanisms of reparation of DNA damage, are showed to be related with the incidence of breast and ovarian cancer, both sporadic and familiar. PARP is a family of enzymes involved in the base excision repair (BER) system. The introduction of inhibitors of PARP in patients with BRCA-mutated ovarian cancer is correlated with the concept of synthetic lethality. Among the PARP inhibitors introduced in clinical practice, niraparib showed interesting results in a phase III trial in the setting of maintenance treatment in ovarian cancer, after platinum-based chemotherapy. Interestingly, was niraparib showed to be efficacious not only in BRCA-mutated patients, but also in patients with other alterations of the homologous recombination (HR) system and in patients with unknown alterations. These results position niraparib as the first PARP-inhibitor with clinically and statistically significant results also in patients with no alterations in BRCA 1/2 and other genes involved in the DNA repair system. Even if the results are potentially practice-changing, the action of niraparib must be further studied and deepened.


Split-Hand Malformation in a 4-Year-Old Child.
Split-hand deformity is one of the milder manifestations of a congenital disorder called split-hand/split-foot malformation. We present a case of a 4-year-old child with split-hand malformation in his left hand since birth. A median cleft was present in the affected hand with absence of the 3rd and 4th digits, giving rise to a characteristic lobster-claw appearance. Functionality of the affected hand was modestly impaired. As none of the close family members of the patient had similar limb malformations, the deformity was postulated to arise most likely from a de novo mutation. The patient was discharged after the parents were provided with genetic counseling.


Immediate bail-out TAP-stenting for the treatment of iatrogenic aortocoronary dissection involving left main bifurcation.
Iatrogenic aortocoronary dissection is a rare but potentially disastrous complication of percutaneous coronary intervention. The left main dissection extending into distal bifurcation involving both the left anterior descending and left circumflex is a complex and vital complication, which is classified as Eshtehardi Type II dissection. We presented a case of iatrogenic left main coronary artery dissection with upcoming closure of both major branches, which was successfully managed by immediate bail-out TAP-stenting. The 77-year-old patient was discharged without any complication, and 1-year follow-up indicated stent patency and favorable clinical result. Immediate bail-out stenting is a feasible and reasonable initial management for this lethal complication.


Molecular Mechanisms of the 1-Aminocyclopropane-1-Carboxylic Acid (ACC) Deaminase Producing Trichoderma asperellum MAP1 in Enhancing Wheat Tolerance to Waterlogging Stress.
Waterlogging stress (WS) induces ethylene (ET) and polyamine (spermine, putrescine, and spermidine) production in plants, but their reprogramming is a decisive element for determining the fate of the plant upon waterlogging-induced stress. WS can be challenged by exploring symbiotic microbes that improve the plant's ability to grow better and resist WS. The present study deals with identification and application of 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase-producing fungal endophyte Trichoderma asperellum (strain MAP1), isolated from the roots of Canna indica L., on wheat growth under WS. MAP1 positively affected wheat growth by secreting phytohormones/secondary metabolites, strengthening the plant's antioxidant system and influencing the physiology through polyamine production and modulating gene expression. MAP1 inoculation promoted yield in comparison to non-endophyte inoculated waterlogged seedlings. Exogenously applied ethephon (ET synthesis inducer) and 1-aminocyclopropane carboxylic acid (ACC; ET precursor) showed a reduction in growth, compared to MAP1-inoculated waterlogged seedlings, while amino-oxyacetic acid (AOA; ET inhibitor) application reversed the negative effect imposed by ET and ACC, upon waterlogging treatment. A significant reduction in plant growth rate, chlorophyll content, and stomatal conductance was noticed, while H2O2, MDA production, and electrolyte leakage were increased in non-inoculated waterlogged seedlings. Moreover, in comparison to non-inoculated waterlogged wheat seedlings, MAP1-inoculated waterlogged wheat exhibited antioxidant-enzyme activities. In agreement with the physiological results, genes associated with the free polyamine (PA) biosynthesis were highly induced and PA content was abundant in MAP1-inoculated seedlings. Furthermore, ET biosynthesis/signaling gene expression was reduced upon MAP1 inoculation under WS. Briefly, MAP1 mitigated the adverse effect of WS in wheat, by reprogramming the PAs and ET biosynthesis, which leads to optimal stomatal conductance, increased photosynthesis, and membrane stability as well as reduced ET-induced leaf senescence.


[Long-term results of conservative treatment of pyo-destructive diseases of the lungs and parapneumonic empyema].
An analysis of results and treatment outcomes of 178 patients has been made. The patients were examined 1, 3, 6, 12, 24 months after discharge from hospital. The parameters characterizing residual cavities, pneumofibrosis, pleural fibrosis and changes in the bronchial tree were analyzed. Recovery was noted in 172 patients (96.63%). According to CT scan data positive dynamics in the reparative processes in the lungs and pleural cavity could be seen. No relapses of the purulent processes and development of lung cirrhosis were noted.


Thiazolidinediones: metabolic actions in vitro.
To unravel the molecular mechanisms and the causal chain of how thiazolidinediones (TZDs) affect glucose homeostasis, it is helpful to analyse their direct influence on isolated specimens of fat, muscle, and liver in vitro. Studies on isolated adipocytes have shown that the nuclear peroxisome proliferator-activated receptor-gamma (PPAR gamma) is an important molecular target for TZDs, through which they trigger adipocyte differentiation and adipose tissue remodelling. It is not clear, however, if the activation of PPAR gamma in adipose tissue is the cause of all the metabolic actions of TZDs. Based on in vitro studies, two hypotheses have been developed. The first emphasizes PPAR gamma-mediated actions on adipose tissue, suggesting that insulin sensitization of skeletal muscle and liver is triggered indirectly by changes in circulating concentrations of adipocyte-derived non-esterified fatty acids and peptide hormones. The second states that TZDs improve glucose homeostasis independently from adipose tissue actions by the direct interaction with muscle and liver. This hypothesis is supported by direct TZD actions on fuel metabolism of skeletal muscle and liver in vitro, which seem to be independent from PPAR gamma signalling. Major progress has been made in understanding the mechanisms involved in the effects of TZDs on adipose tissue but the causal chain responsible for their antihyperglycaemic action is still not clear. The involvement of other molecular targets in addition to PPAR gamma, of adipocyte-derived messengers, and of direct interaction with skeletal muscle and liver have yet to be clarified.


Inverted, T-shaped silicone implant for the treatment of temporomandibular joint ankylosis.
Reconstruction of the ankylosed temporomandibular joint is a challenging task. Speech impairment, difficulties with mastication, poor oral hygiene, facial asymmetry, and mandibular micrognathia results in physical and psychologic disabilities. Various surgical techniques with varying success rates have been reported. Many autogenous and alloplastic materials have been proposed. The authors used an inverted, T-shaped silicone implant for the reconstruction of the temporomandibular joint after the release of the ankylosis in 10 patients without any complications in the postoperative period. The authors assert that the reconstruction of the ankylosed temporomandibular joint with an inverted, T-shaped silicone implant is a reliable and effective alternative. This technique can be used according to the special requirements of each patient and obviating the need for the fixation of the implant and is a safer and better way of using silicone for the treatment of temporomandibular joint ankylosis.


Alcohol policy and the young adult: establishing priorities, building partnerships, overcoming barriers.
Young adults (defined here as those 18-29 years of age) in the United States and Canada constitute a demographic group most likely to suffer serious alcohol problems, yet the alcohol policy field has made little effort to develop prevention strategies that respond specifically to their circumstances and needs. This paper briefly reviews relevant research, analyzes prevention policy priorities, presents the barriers to implementation and outlines strategies for overcoming them. Its main conclusions are: (1) Strategies to reduce alcohol availability and increase alcohol prices will significantly reduce alcohol problems among young adults. (2) A high priority should be given to harm reduction strategies and strategies that target the physical environments where young adults are likely to congregate. (3) The alcohol industries and the industries' allies will vigorously oppose these policy reforms, and their resistance constitutes a formidable barrier to implementation. (4) Resistance from other community institutions, which may benefit from the status quo, is an additional barrier that must be addressed. (5) There is a tendency to compromise with the alcohol industries and others and substitute individual-based prevention strategies for public policy reforms. Individual-based strategies complement public policy reforms but should not replace them. (6) Overcoming barriers will require community organizing, coalition building, media advocacy and policy advocacy and an expanded research effort. The field needs to develop new messages and themes in both media and policy advocacy that address the specific concerns and interests of young adults, thereby encouraging their active leadership in prevention policy development.


Educational workshop with adolescents on leprosy: case report.
To report the experience of professors and students in the development and implementation of an educational workshop on leprosy with adolescents. Method: This is a case report from actions contained in a university extension project. The workshop program was elaborated with duration of two hours, including five dynamic techniques adapted to the topic: adjective, face, traffic light, true or false and mosaic. It was verified that the construction of knowledge in light of the verbalization of the adolescents and the interest in working in the society they live through sharing this knowledge, especially those who were more involved in the process. It was concluded that the applied workshops enabled building knowledge and demystifying myths and stigmas socially constructed to adolescents, as well as allowed Nursing students to experience educational interventions on leprosy with adolescents.


Clinical short-term results of radiofrequency ablation in primary and secondary liver tumors.
Radiofrequency ablation (RFA) is emerging as a new therapeutic method for management of solid tumors. We report here our experience in the use of this technique for management of primary and secondary unresectable liver cancers. Thirty-five patients with liver cancers were considered not suitable for curative resection at presentation: 8 with primary hepatocellular carcinoma ([HCC] 6 HCC and 2 fibrolamellar); 27 with metastatic liver cancer (17 colorectal carcinoma and 10 others). They were treated either with radiofrequency heat ablation (Radionics Europe N.V., Wettdren, Belgium) alone percutaneously and/or intraoperatively or in conjunction with surgical resections. The quality of RFA was based on the subjective feeling of whether the tumor was completely destroyed or not. The effectiveness of RFA was assessed according to clinical findings, radiographic images, and tumor markers at follow-up. In 8 primary liver cases, 4 patients with a high level of alpha fetoprotein (AFP) benefited from the RFA with a 83.3% to 99.7% reduction of AFP. One with fibrolamellar hepatocellular carcinoma died 2 months after an incomplete percutaneous RFA from recurrence. The rest all had stable disease at the time of follow-up (mean 10.4 months). In patients with colorectal liver metastases, there were 4 deaths: 1 patient died postoperatively on the 30th day from a severe chest infection having shown a considerable reduction of carcinoembryonic antigen level (CEA, 8 versus 36 microg/L); 3 died from local and systemic disease, 1 at 12 months and 2 at 1 month, having had an incomplete RFA. The others had stable disease at follow-up (mean 7.6 months). Five patients underwent liver resections successfully with the application of RFA for residual lesions in the remaining contralateral lobe. In 10 patients with other liver tumors, 7 patients had stable disease at follow-up (mean 13.4 months); 1 patient had evidence of local and systemic recurrence 10 months after surgical resections with the intraoperative RFA and 2 patients died of systemic recurrence of disease 3 and 6 months after RFA alone. Two patients had liver resections in conjunction with the intraoperative RFA. The mean follow-up in our series was 8.5 months. Radiofrequency heat ablation is useful as a primary treatment for unresectable liver cancers. The procedure can be used to treat the small residual tumor load in the contralateral lobe following liver resection in those considered unresectable at the first presentation. This new therapeutic strategy seems to increase surgical resectability in patients judged unresectable.


LSD1 demethylates histone and non-histone proteins.
One of the key breakthroughs in the epigenetics/chromatin field in the last several years was the identification of enzymes capable of removing the methyl group from methylated lysines in histone proteins. Lysine-specific demethylase 1 (LSD1) was the first such enzyme identified, which has been shown to demethylate histone H3 on lysine 4 (H3K4) and lysine 9 (H3K9). LSD1 is essential for mammalian development and likely involved in many biological processes. Recent studies show that LSD1 demethylates p53 and Dnmt1 and regulates their cellular functions, indicating that LSD1 fulfills its biological functions by directly acting on both histone and non-histone proteins. LSD1 contains several defined domains and associates with a number of protein complexes. Interacting partners of LSD1 may play key roles in determining/modulating the activity and specificity of LSD1.


The submariners' sleep study: a field investigation of sleep and circadian hormones during a 67-day submarine mission with a strict 6-h-on/6-h-off watch routine.
The submarine working and living environment is an isolated, confined, and extreme (ICE) environment where a continuous on-watch is required to fulfill the tactical objectives. The current study examined whether a physiological and behavioral adjustment to an operational watch standing scheme occurred in terms of hormonal secretion (i.e., melatonin and cortisol) and sleep during a 67-day undersea mission. The crew followed a strict scheme of watch-on blocks at 0:00-06:00 h and at 12:00-18:00 h (group 1, diurnal sleep group) or watch-on blocks at 06:00-12:00 h and 18:00-24:00 h (group 2, nocturnal sleep group). We sampled saliva during the operational blocks over a 24-h period at day 55 of the mission and collected sleep actigraphy data during the entire mission in 10 participants. Sleep showed a biphasic split pattern with significantly unequal distributions of total sleep time (TST) and sleep efficiency (SE) between the two sleeping blocks, i.e., one long and one short sleep bout. Melatonin secretion showed no adjustment at the end of the mission to the watch standing blocks, following an endogenous circadian rhythm independent from the social zeitgebers with indications of a phase shift. Cortisol secretion however matched the biphasic work-sleep shift routine. Human physiology does not fully obey operational needs and there are differences in adjustment between melatonin and cortisol. A watch standing schedule that provides a balance between physiology and operationality still needs to be established. The potential adaptation effects of bright light therapy and melatonin supplementation should be investigated in future research.NEW & NOTEWORTHY The current study has a unique character due to the field context in which the data were collected. Data on long-term submarine missions are scarce and valuable in terms of operational and ecological validity. Moreover, the results are important both from a scientific and operational point of view, showing that human physiology does not fully obey operational needs and that there are differences in adjustment dependent from the type of circadian hormone.


Feasibility study on donor apheresis red cell and platelet simultaneous collection for blood center routine use.
This study was conducted to determine if single donor platelet and red cell simultaneous collection by apheresis technique can be applied to routine blood product collection at blood centers. Both apheresis red cell product and platelet product were successfully collected and mannitol, adenine, and phosphate (MAP) additive solution was added to the red cell concentrates during collection. During a 49 day storage study period, the red cell product quality was maintained and found to be equivalent to that of red cell products derived from whole blood collected by the traditional method. This study demonstrated the possibility of applying this collection method for routine use for single donor apheresis platelet product and red cell product preparation at blood centers.


Dialysis for acute kidney injury associated with influenza a (H1N1) infection.
In June 2009, the World Health Organization declared a novel influenza A, S-OIV (H1N1), pandemic. We observed 44 consecutive patients during the "first wave" of the pandemic. 70.5% of them showed co-morbidities (hypertension, obesity, chronic respiratory diseases, chronic renal disease, diabetes, pregnancy). Serious cases were admitted to the intensive care unit (ICU), particularly those with severe acute respiratory failure. Some of them developed acute kidney injury (AKI) and required renal replacement therapy (RRT). The average time between admission to the ICU and initiation of RRT was 3.16 ± 2.6 days. At initiation of RRT, most patients required mechanical ventilation. No relationship was found with creatinine-kinase levels. Seventy-five percent of the cases were observed during a 3-week period and mortality, related to respiratory failure, doubling of alanine amino transferase and use of inotropics was 81.8%. In conclusion, the H1N1-infected patients who developed RRT-requiring AKI, in the context of multi-organ failure, showed a high mortality rate. Thus, it is mandatory that elaborate strategies aimed at anticipating potential renal complications associated to future pandemics are implemented.


A novel pyrrole synthesis.
The silver(I)-promoted oxidative cyclization of homopropargylamines at room temperature provides a novel access to pyrroles. Homopropargylamines are readily available by the addition of a propargyl Grignard reagent to Schiff bases.


[Cocaine abuse--with special reference to cerebrovascular complications].
The role of drug abuse as a risk factor for cerebrovascular events has been underestimated, particularly in patients with juvenile stroke. The drug most often associated with acute cerebrovascular events is cocaine. After cocaine hydrochloride abuse intracerebral hemorrhages or subarachnoid hemorrhages--predominantly caused by ruptured aneurysms or arteriovenous malformations--are by far the most frequently observed cerebrovascular complications, whereas on abuse with the alkaloidal form ("crack") intracranial hemorrhages and ischemic strokes are encountered with equal frequency. In most cases, the time interval between drug abuse and the cerebrovascular event is less than 3 hours. Several pathophysiological mechanisms are discussed as serving as triggers for the cerebrovascular event, either alone or in combination. No specific antidote to cocaine is known. Nevertheless drug screening (urine analysis) should be performed immediately to allow optimal management of patients with drug-associated acute cerebrovascular events, especially in cases with juvenile stroke.