Lin28a protects against hypoxia/reoxygenation induced cardiomyocytes apoptosis by alleviating mitochondrial dysfunction under high glucose/high fat conditions.
The aim of the present study was to investigate the role of Lin28a in protecting against hypoxia/reoxygenation (H/R)-induced cardiomyocytes apoptosis under high glucose/high fat (HG/HF) conditions. Primary cardiomyocytes which were isolated from neonatal mouse were randomized to be treated with lentivirus carrying Lin28a siRNA, Lin28acDNA 72 h before H/R (9 h/2 h). Cardiomyocytes biomarkers release (LDH and CK), cardiomyocytes apoptosis, mitochondria biogenesis and morphology, intracellular reactive oxygen species (ROS) production, ATP content and inflammatory cytokines levels after H/R injury in high glucose/high fat conditions were compared between groups. The target proteins of Lin28a were examined by western blot analysis. Our results revealed that Lin28a cDNA transfection (overexpression) significantly inhibited cardiomyocyte apoptotic index, improved mitochondria biogenesis, increased ATP production and reduced ROS production as compared with the H/R group in HG/HF conditions. Lin28a siRNA transfection (knockdown) rendered the cardiomyocytes more susceptible to H/R injury as evidenced by increased apoptotic index, impaired mitochondrial biogenesis, decreased ATP production and increased ROS level. Interestingly, these effects of Lin28a were blocked by pretreatment with the PI3K inhibitor wortmannin. Lin28a overexpression increased, while Lin28a knockdown inhibited IGF1R, Nrf-1, Tfam, p-IRS-1, p-Akt, p-mTOR, p-p70s6k, p-AMPK expression levels after H/R injury in HG/HF conditions. Moreover, pretreatment with wortmannin abolished the effects of Lin28a on the expression levels of p-AKT, p-mTOR, p-p70s6k, p-AMPK. The present results suggest that Lin28a inhibits cardiomyocytes apoptosis by enhancing mitochondrial biogenesis and function under high glucose/high fat conditions. The mechanism responsible for the effects of Lin28a is associated with the PI3K/Akt dependent pathway.


Effect of nortriptyline and paroxetine on CYP2D6 activity in depressed elderly patients.
This study was performed in elderly patients (1) to assess the degree to which CYP2D6 mediated metabolism of debrisoquine at baseline determines plasma concentration to dose quotients for nortriptyline or paroxetine after 4 weeks of treatment, and (2) to compare the effects of nortriptyline and paroxetine on debrisoquine metabolism after 6 weeks of treatment. CYP2D6 activity was estimated in 66 subjects (71.4 +/- 7.2 years) before initiating treatment and again after 6 weeks of treatment with either nortriptyline or paroxetine under randomized, double-blind conditions according to a standard protocol. CYP2D6 activity was estimated by the debrisoquine recovery ratio in a 6- to 8-hour urine sample collected after oral administration of 10 mg debrisoquine sulfate. Nortriptyline and paroxetine plasma concentrations were obtained weekly. Baseline debrisoquine recovery ratio values were significantly correlated with the plasma concentration to dose quotient at 4 weeks for both nortriptyline ( = -0.75, = 0.0001, N = 29) and paroxetine ( = -0.50, = 0.003, N = 33). Treatment with either nortriptyline or paroxetine was associated with a significant decrease in the median debrisoquine recovery ratio, reflecting inhibition of CYP2D6 metabolism. The percent decrease associated with nortriptyline was significantly smaller than that with paroxetine ( < 0.0001). None of the patients treated with nortriptyline but 19 of the 32 extensive metabolizers treated with paroxetine were converted to phenotypic poor metabolic status. Our observations of CYP2D6 inhibition are consistent with data and results obtained in younger healthy volunteers. The significant correlations between baseline debrisoquine recovery ratio and the plasma concentrations to dose quotients at 4 weeks for both nortriptyline and paroxetine are consistent with CYP2D6 playing a major role in the metabolism of both drugs. CYP2D6 inhibition by paroxetine, which effectively converted 59% of patients to phenotypic PMs, may be especially relevant for elderly patients given their generally higher concentration of paroxetine.


Detection of the mcr-1 gene in colistin-resistant Escherichia coli from retail meat in Japan.
In this study, the presence of the mcr-1 gene in Escherichia coli from retail meat in Japan was investigated. Nine E. coli isolates (eight from chickens and one from pork) carried the mcr-1 gene on the plasmid. In six isolates from domestic chickens, mcr-1 was located on the IncI2 plasmid, which is approximately 60 kb in size. In the remaining three isolates from imported chicken and pork, mcr-1 was located on the IncX4 plasmid (30 kb).


Analysis of HIV-1 reverse transcriptase and protease sequences in paired plasma and lymphoid tissue specimens from HIV-1 infected individuals.
To determine how representative the genotype of HIV-1 circulating in plasma is of the genotype of the virus present in lymphoid tissue. Paired plasma and tonsillar tissue samples were prospectively obtained from patients with various levels of plasma HIV-1 RNA who were receiving combination antiretroviral therapy. HIV-1 reverse transcriptase and protease sequences were amplified from plasma and lymphoid tissue specimens by nested polymerase chain reaction and analyzed using an automated sequencing system. Results were compared with consensus HIV-1 sequences to determine whether drug-resistance mutations were present in the regions analyzed. HIV-1 protease sequences were compared in 11 plasma/tissue pairs obtained from eight patients; HIV reverse transcriptase sequences were compared in 12 plasma/tissue pairs obtained from nine patients. Sequence homology between plasma and tissue RNA, tissue RNA and DNA, and plasma and tissue DNA ranged from 97% to 100%. Few discrepancies were found when the percentage of mutant sequences at resistance codons was compared among paired samples. In most instances, tissue RNA or plasma contained a higher percentage of mutant sequences than did tissue DNA. The genotype of plasma HIV-1 is similar to the genotype of the virus in lymphoid tissue. Resistance studies using plasma samples should provide accurate information regarding the genotype of HIV-1 in lymphoid tissues.


Immunohistochemical evidence for the presence of tumor necrosis factor-alpha in the infant and adult human ovary.
The cytologic localization and cellular levels of tumor necrosis factor-alpha (TNF alpha) in the human ovary during follicular growth and regression were examined by the avidin/biotin immunoperoxidase method with a specific antibody to human recombinant TNF alpha. In the infant ovary, TNF alpha immunostaining was present only in the oocyte within the primordial follicles. TNF alpha immunostaining was also present within the oocyte in primordial follicles of the adult ovary. Positive immunostaining for TNF alpha in granulosa cells became apparent in preantral follicles, while that in theca interna cells began to appear at the antral follicle stage. The staining intensity of the oocyte increased as the oocyte reached the preovulatory stage. The intensity of immunostaining for TNF alpha in the granulosa and thecal cells increased as the follicle became larger and matured. In corpora lutea, the immunostaining for TNF alpha persisted in the granulosa lutein and theca lutein cells and intensified in the mid luteal phase. In the regressing corpora lutea, TNF alpha immunostaining in the luteal cells decreased as the regression advanced. Regressed corpora lutea with a central core of scar tissue were bordered by macrophage-like cells which exhibited intense immunostaining for TNF alpha. In the cortex region, the corpus albicans was negative for TNF alpha immunostaining, whereas macrophage-like cells peripheral to the corpus albicans exhibited intense immunostaining for TNF alpha. In the medullary region, the corpus albicans and surrounding stromal cells were totally negative for TNF alpha. By contrast, in the early atretic stage, the degenerating oocyte showed weak immunostaining for TNF alpha, while the granulosa and theca interna cells showed moderate immunostaining for TNF alpha. In the late atretic stage, the immunostaining for TNF alpha in the scattered granulosa cells became negligible, whereas the theca interna cells showed intense immunostaining for TNF alpha. The results obtained indicate that the oocyte is the primary intrafollicular site of TNF alpha localization within the ovary and that TNF alpha may participate in regulating follicular growth, regression and atresia.


CHARACTERIZATION OF AN ACTIVE DOSEMETER ACCORDING TO IEC 61526:2010.
The active personal dosemeter, RaySafe i2, allows the measurement and record of Hp(10) in real time, every second, via wireless technology for real-time display on a portable computer and/or a local network. The system seems particularly attractive for individual monitoring at clinical facilities where high intensity and varying radiation fields may occur, as it enables the user to acknowledge and optimize the dose and dose rate values in real time for each procedure. Prior to its use, the system was characterized at the Metrology Laboratory of Ionizing Radiation of IST-LPSR aiming at the metrological characterization of the system in accordance with IEC 61526:2010 for metrological control purposes and to verify the technical specifications stated by the manufacturer.


Positioning Combination Method of USBL Using Four-Element Stereo Array.
In the present article, an ultra-short baseline (USBL) combined location method based on three four-element stereo arrays is proposed. In order to solve the problem of the poor positioning effect of acoustic positioning under a high incident angle of signal, two kinds of four-element stereo arrays are designed, and the localization approach of the new array is given. At the same time, for the regular triangular pyramid array, a virtual array element is proposed to construct a planar cross array to improve the poor positioning effect of the regular triangular pyramid array at a low incident angle. This paper analyzes the positioning performance of three arrays. Combined with the traditional cross-planar array localization method, a set of positioning strategies to switch the two localization methods under different incident angles were designed. The switching thresholds of the two methods were analyzed by simulation. Simulation results show that the new arrays can locate stably at different incident angles and improve the overall positioning performance of the array.


Epigenetic mechanisms of drug addiction.
Drug addiction involves potentially life-long behavioral abnormalities that are caused in vulnerable individuals by repeated exposure to a drug of abuse. The persistence of these behavioral changes suggests that long-lasting changes in gene expression, within particular regions of the brain, may contribute importantly to the addiction phenotype. Work over the past decade has demonstrated a crucial role for epigenetic mechanisms in driving lasting changes in gene expression in diverse tissues, including brain. This has prompted recent research aimed at characterizing the influence of epigenetic regulatory events in mediating the lasting effects of drugs of abuse on the brain in animal models of drug addiction. This review provides a progress report of this still early work in the field. As will be seen, there is robust evidence that repeated exposure to drugs of abuse induces changes within the brain's reward regions in three major modes of epigenetic regulation-histone modifications such as acetylation and methylation, DNA methylation, and non-coding RNAs. In several instances, it has been possible to demonstrate directly the contribution of such epigenetic changes to addiction-related behavioral abnormalities. Studies of epigenetic mechanisms of addiction are also providing an unprecedented view of the range of genes and non-genic regions that are affected by repeated drug exposure and the precise molecular basis of that regulation. Work is now needed to validate key aspects of this work in human addiction and evaluate the possibility of mining this information to develop new diagnostic tests and more effective treatments for addiction syndromes. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.


Tracing the Biotransformation of PCBs and PBDEs in Common Carp (Cyprinus carpio) Using Compound-Specific and Enantiomer-Specific Stable Carbon Isotope Analysis.
Compound-specific and enantiomer-specific carbon isotope composition was investigated in terms of biotransformation of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) as well as atropisomers of chiral PCB congeners in fish by exposing common carp (Cyprinus carpio) to certain PCB and PBDE congeners. The calculated carbon isotope enrichment factors (εC) for PCB 8, 18, and 45 were -1.99, -1.84, and -1.70‰, respectively, providing evidence of the metabolism of these congeners in fish. The stable carbon isotopic compositions of PBDE congeners clearly reflect the debromination of PBDEs in carp. Significant isotopic fractionation was also observed during the debromination process of BDE 153 (εC = -0.86‰). Stereoselective elimination of chiral PCB congeners 45, 91, and 95 was observed, indicating a stereoselective biotransformation process. The similar εC values for E1-PCB 45 (-1.63‰) and E2-PCB 45 (-1.74‰) indicated that both atropisomers were metabolized by the same reaction mechanisms and stereoselection did not occur at carbon bond cleavage. However, the εC values of (+)-PCB 91 (-1.5‰) and (-)-PCB 95 (-0.77‰) were significantly different from those of (-)-PCB 91 and (+)-PCB 95, respectively. In the latter, no significant isotopic fractionations were observed, indicating that the stereoselective elimination of PCB 91 and 95 could be caused by a different reaction mechanism in the two atropisomers.


Inferior orbital septum release compared with lateral canthotomy and cantholysis in the management of orbital compartment syndrome.
The purpose of this study is to assess the utility of inferior orbital septum release compared with lateral canthotomy and inferior cantholysis for the treatment of orbital compartment syndrome. An experimental study design using a cadaver model for orbital compartment syndrome was used to compare the efficacy of inferior orbital septum release with lateral canthotomy and inferior cantholysis. Elevated orbital compartment pressures were created in a total of 10 orbits of 5 fresh cadaver heads. Compartment pressure and intraocular pressure were measured before and after inferior orbital septum release and lateral canthotomy/cantholysis. Additionally, orbital compartment pressure was compared with intraocular pressure at various pressures to assess correlation. Statistical analysis was performed on the collected data for efficacy comparison of the 2 procedures. Both procedures were found significantly to reduce orbital compartment pressure. Lateral canthotomy and cantholysis was found to lower the pressure by an average of 56 mm Hg as compared with inferior septal release, which resulted in an average of 52-mm Hg reduction. Performing lateral canthotomy and cantholysis first, followed by inferior septal release, resulted in a total pressure reduction of 73 mm Hg, whereas reversing the order resulted in a reduction of 77 mm Hg. Both the first and second steps, regardless of the order of procedure, were found to result in a significant pressure reduction (p = 0.009 and 0.004, respectively). Comparison of a series of data points collected during the induction of the experimental compartment syndrome revealed a statistically significant correlation between orbital compartment pressure and intraocular pressure (Spearman correlation of 0.978 and p value <0.001). The study demonstrates that both lateral canthotomy/cantholysis and inferior orbital septum release are equally effective at reducing orbital compartment pressure. Additionally, the data support an additive, synergistic reduction in compartment pressure when the procedures are performed consecutively. The correlation of orbital compartment pressure to intraocular pressure proves that intraocular pressure can be used as a reliable measurement of orbital pressure during acute changes in orbital mass. The results of this study demonstrate that the use of inferior orbital septum release in conjunction with lateral canthotomy and cantholysis is superior to the gold standard of isolated lateral canthotomy and cantholysis. We hope that the implementation of orbital septum release will result in superior visual outcomes.


Prediction of gene function by genome-scale expression analysis: prostate cancer-associated genes.
We wish to identify genes associated with disease. To do so, we look for novel genes whose expression patterns mimic those of known disease-associated genes, using a method we call Guilt-by-Association (GBA), on the basis of a combinatoric measure of association. Using GBA, we have examined the expression of 40,000 human genes in 522 cDNA libraries, and have discovered several hundred previously unidentified genes associated with cancer, inflammation, steroid-synthesis, insulin-synthesis, neurotransmitter processing, matrix remodeling, and other disease processes. The majority of the genes thus discovered show no sequence similarity to known genes, and thus could not have been identified by homology searches. We present here an example of the discovery of eight genes associated with prostate cancer. Of the 40,000 most-abundant human genes, these 8 are the most closely linked to the known diagnostic genes, and thus are prime targets for pharmaceutical research.


Effect of vanadate on the chromatin configuration in pig GV-oocytes.
Vanadate, an inhibitor of tyrosine phosphatases, has been reported to prevent germinal vesicle breakdown in mammalian oocytes. We examined the effect of vanadate on the chromatin configuration of fully grown pig oocytes. In the presence of human menopausal gonadotropin (hMG), vanadate (0.5-5 mM) resulted in a dose-dependent change in oocyte chromatin in germinal vesicles from the condensed state to a decondensed filamentous or stringy configuration. The effect of vanadate and hMG on chromatin configuration could be replicated with 2 mM dibutyryl cyclic AMP (dbcAMP) in place of hMG. Western blot analysis showed that vanadate caused a massive accumulation in the oocytes of tyrosine-phosphorylated proteins with a range of molecular weights that was enhanced by both hMG and dbcAMP in a similar manner. These results suggest that inhibition of tyrosine phosphatase(s) in the presence of an effective level of cAMP induces a change in chromatin configuration of pig oocytes.


Evidence for antigen presentation to sensitized T cells by thyroid peroxidase (TPO)-specific B cells in mice injected with fibroblasts co-expressing TPO and MHC class II.
Injection of AKR/N mice with fibroblasts co-expressing MHC class II and TPO in the absence of adjuvant induces IgG-class TPO antibodies that resemble spontaneously arising human thyroid autoantibodies. We have used this model to examine the effect of iodide on TPO antibody induction as well as to analyse the interaction between T and B cells. Despite its importance as a major environmental factor in thyroid autoimmunity, variable iodide intake had no detectable effects on TPO antibody levels, lymphocytic infiltration of the thyroid or thyroid hormone levels. In terms of T cell responsiveness, splenocytes from TPO fibroblast-injected mice, but not from control mice, proliferated in response to TPO. Intriguingly, B cell-depleted splenocytes (mainly T cells without reduction of macrophages) proliferated in response to TPO only when co-cultured with irradiated autologous splenocytes from TPO fibroblast-injected mice but not from control mice. These data suggest that TPO-specific B cells are involved in antigen presentation to sensitized T cells and are supported by the ability of spleen cells from TPO cell-injected (but not control) mice to secrete TPO antibodies spontaneously in culture. In conclusion, we provide the first evidence for the presence of thyroid autoantigen-specific B cells and their ability to present their autoantigen to sensitized T cells in mice induced to develop TPO antibodies resembling autoantibodies in humans.


How Does the Number of Response Options Impact the Psychometric Properties of the Rosenberg Self-Esteem Scale?
The Rosenberg Self-Esteem Scale is the most frequently used measure of self-esteem in the social sciences. These items are often administered with a different number of response options, but it is unclear how the number of response options impacts the psychometric properties of this measure. Across three experiments (Ns = 739, 2,358, and 1,461), we evaluated how different response options of the Rosenberg influenced (a) coefficient alpha estimates, (b) distributions of scores, and (c) associations with criterion-related variables. Observed coefficient alpha estimates were lowest for a 2-point format compared with response formats with more options. However, supplemental analyses using ordinal alpha pointed to similar estimates across conditions. Using four or more response options better approximated a normal distribution for observed summary scores. We found no consistent evidence that criterion-related correlations increased with more response options. Collectively, these results suggest that the Rosenberg should be administered with at least four response options and we favor a 5-point Likert-type response format.


Thromboxane production in copper-deficient and marginal platelets: influence of superoxide dismutase and lipid hydroperoxides.
Platelet thromboxane (TX) production was examined in response to dietary copper. Groups of eight rats were fed copper-deficient, -marginal, and -adequate diets providing 0.5, 1.7, and 7.5 micrograms Cu/g, respectively, with controlled dietary Se and vitamin E. Platelets were purified and washed by centrifugation. Separate platelet samples from each rat were challenged with 10 micrograms/ml of collagen and 1 unit/ml (27.3 nM) of thrombin in Tyrode's buffer, 2.0 mM Ca2+. Platelet copper-dependent superoxide dismutase (CuSOD) activity showed a significant depression with reduced diet copper, but platelet glutathione peroxidase activity was unaffected. Challenged platelet TX production showed a significant 1.5- to 2.5-fold increase in response to both dietary copper deficiency and marginality, with highly significant negative correlations between challenged platelet TX production and platelet CuSOD activity and between TX production and copper status (liver copper). Endogenous (unchallenged) platelet lipid hydroperoxide concentrations, measured as free fatty acid hydroperoxides by a glutathione-disulfide-specific glutathione reductase recycling assay, showed a nonsignificant 47-67% increase in copper deficiency. Pooled data showed a significant 71% increase in platelet lipid hydroperoxides in copper deficiency. Platelet TX production showed a significant correlation with endogenous lipid hydroperoxides. The results suggest that dietary copper insufficiency increases platelet TX synthesis through changes in CuSOD in a dose-responsive (diet copper and platelet CuSOD activity) manner, and that platelet TX synthesis is influenced by lipid hydroperoxides (peroxide tone).


[Motivation on plaque control and gingival bleeding in school children].
The objective of the study is to evaluate the impact of two pedagogical motivational approaches for plaque and gingival bleeding control among 135 students of local public schools in Santa Tereza, Brazil, in 1999 The motivational program consisted of different educational strategies offered to two distinct groups: Group A, who attended only one explanatory session about oral hygiene, and Group B, who attended a total of four pedagogical sessions. In order to evaluate the methodology applied, the visible plaque index (according to Ainamo & Bay, 1975) and gingival bleeding index (according to L e and Silness, 1963) were calculated. A highly statistically significant reduction in the visible plaque index and gingival bleeding index was observed in both groups after the educational sessions (p<0.001). Moreover, a higher reduction in the gingival bleeding index and an even more accentuated decrease in the visible plaque index was found in group B when compared to group A (p<0.001). In conclusion, the motivational reinforcement in educational and preventive programs has a positive effect for the reduction and control of gingival bleeding and bacterial plaque.


A simulation-based intervention teaching seizure management to caregivers: A randomized controlled pilot study.
To examine the effect of simulation-based seizure management teaching on improving caregiver competence and reported confidence with managing seizures. The authors hypothesized that simulation-based education would lead to a higher level of demonstrated competence and reported confidence in family members and caregivers. Simulation has not been previously studied in this context. A two-group pre- and post-test experimental research design involving a total of 61 caregivers was used. The intervention was a simulation-based seizure curriculum delivered as a supplement to traditional seizure discharge teaching. Caregiver performance was analyzed using a seizure management checklist. Caregivers' perception of self-efficacy was captured using a self-efficacy questionnaire. Caregivers in the experimental group achieved significantly higher postintervention performance scores than caregivers in the control group in both premedication and postmedication seizure management (P<0.01). Additionally, they achieved significantly higher scores on the self-efficacy questionnaire including items reflecting confidence managing the seizure at home (P<0.05). Caregivers receiving the supplemental simulation-based curriculum achieved significantly higher levels of competence and reported confidence, supporting a positive relationship between simulation-based seizure discharge education, and caregiver competence and confidence in managing seizures. Simulation sessions provided insight into caregiver knowledge but, more importantly, insight into the caregiver's ability to apply knowledge under stressful conditions, allowing tailoring of curriculum to meet individual needs. These findings may have applications and relevance for management of other acute or chronic medical conditions.


Synthesis, Structure, and Function of Human Adenovirus Small Non-Coding RNAs.
Human adenoviruses (HAdVs) are common pathogens causing a variety of respiratory, ocular and gastrointestinal diseases. To accomplish their efficient replication, HAdVs take an advantage of viral small non-coding RNAs (sncRNAs), which have multiple roles during the virus lifecycle. Three of the best-characterized HAdV sncRNAs; VA RNA, mivaRNA and MLP-TSS-sRNA will be discussed in the present review. Even though VA RNA has been extensively characterized during the last 60 years, this multifunctional molecule continues to surprise us as more of its structural secrets unfold. Likely, the recent developments on mivaRNA and MLP-TSS-sRNA synthesis and function highlight the importance of these sncRNA in virus replication. Collectively, we will summarize the old and new knowledge about these three viral sncRNAs with focus on their synthesis, structure and functions.


Comparison of Mycoplasma arthritidis strains by enzyme-linked immunosorbent assay, immunoblotting, and DNA restriction analysis.
Twenty Mycoplasma arthritidis strains or isolates were compared by a combination of enzyme-linked immunosorbent assay by an antiserum adsorption technique, Western immunoblotting, and restriction analysis of chromosomal DNA. Antigenic markers that defined strains related to strains 158p10p9, PG6, and H606 were identified. In addition, restriction analysis allowed all 20 strains to be divided into six groups. Results of restriction analysis corresponded generally with antigenic similarities, although the former did not allow grouping with as fine a precision as the latter. However, intrastrain antigenic variability, which is common among many Mycoplasma species, including M. arthritidis, introduced a complicating factor into our attempts at antigenic analysis. While serologic and antigenic analyses remain useful, we recommend that they be used with caution and in combination with other techniques for identifying and characterizing new isolates and newly acquired strains. Combinations of these techniques have proven to be useful in our laboratory for quality control and for uncovering interesting relationships among strains subjected to animal passage and their less virulent antecedents and among strains originally classified as the same but obtained from different sources and maintained, sometimes for decades, in different laboratories.


Protective effect of quercetin against intracerebral streptozotocin induced reduction in cerebral blood flow and impairment of memory in mice.
The aim of the present study is to investigate the effect of quercetin, a naturally occurring flavonoid, on cerebral blood flow (CBF), brain energy metabolism, memory impairment, oxidative stress and cholinergic dysfunction in brain following intracerebral (i.c.) streptozotocin (STZ) administration in mice. STZ (0.5mg/kg, i.c.) was administered twice at an interval of 48h. We found a significant reduction in CBF as measured by Laser Doppler Flowmetry (LDF). The brain energy metabolism was also altered as evidenced by significant reduction in brain ATP content. Daily treatment with quercetin (2.5, 5 and 10mg/kg, p.o.) starting from the first dose of STZ showed a dose-dependent restoration of CBF and ATP content. Further, quercetin prevented STZ induced memory impairment as assessed by Morris water maze and passive avoidance tests. Biochemical analysis revealed that STZ significantly increased malondialdehyde (MDA), nitrite and depleted glutathione (GSH) levels in the mice brain. Quercetin decreased oxidative and nitrosative stress as evidenced by a significant decrease in MDA, nitrite and increase in GSH levels. Quercetin also attenuated elevated acetylcholinesterase activity in the STZ-treated mice. Neither STZ (i.c.) nor quercetin showed any change in locomotor activity and blood glucose level. The present study demonstrates the beneficial effects of quercetin in improving CBF along with preventing memory impairment, oxidative stress, altered brain energy metabolism and cholinergic dysfunction caused by STZ in mice. Therefore, consumption of dietary stuff rich in quercetin should be encouraged to ward off dementia associated with vascular and neurodegenerative disorders.


A compact tunable diode laser absorption spectrometer to monitor CO2 at 2.7 μm wavelength in hypersonic flows.
Since the beginning of the Mars planet exploration, the characterization of carbon dioxide hypersonic flows to simulate a spaceship's Mars atmosphere entry conditions has been an important issue. We have developed a Tunable Diode Laser Absorption Spectrometer with a new room-temperature operating antimony-based distributed feedback laser (DFB) diode laser to characterize the velocity, the temperature and the density of such flows. This instrument has been tested during two measurement campaigns in a free piston tunnel cold hypersonic facility and in a high enthalpy arc jet wind tunnel. These tests also demonstrate the feasibility of mid-infrared fiber optics coupling of the spectrometer to a wind tunnel for integrated or local flow characterization with an optical probe placed in the flow.


Nutritional consulting in regular veterinary practices in Belgium and the Netherlands.
Increased interest in nutrition by dog and cat owners stresses the importance of providing tailored nutritional guidance for each patient by veterinarians. The World Small Animal Veterinary Association (WSAVA) has provided guidelines to help veterinarians implement this in every-day patient care, by screening patients for the presence of nutritional risk factors, establishing tailored nutritional plans and providing adequate patient follow-up tools. This study aimed to assess the use of nutritional assessments in companion animal practices, and to investigate differences between Dutch and Belgian veterinarians. A survey was conducted among Dutch and Belgian veterinarians. Of the 423 respondents, 53% were from Belgium, and 47% were from the Netherlands. Only 21% had prior knowledge of the WSAVA nutritional assessment guidelines. General trends in the usage of nutritional assessments were similar in the examined countries. Aside from weighing, diet evaluation by collecting dietary information and body condition or muscle condition scoring were used infrequently, mostly due to insufficient knowledge of the methods. Nutritional recommendations were often made as part of a treatment plan, and were mostly made by veterinarians, but in Dutch practices also by veterinary nurses. Despite the fact that nutritional recommendations are a regular part of treatment plans, nutritional risk factors may be missed due to a lack of completely performed nutritional assessments. It remains important to promote the benefits of regular nutritional assessments to veterinarians, which will improve patients' health.


The anxiety of not knowing: Diagnosis uncertainty about COVID-19.
The emergence and swift global spread of COVID-19 brought increased anxiety worldwide (Santabárbara et al. (Progress in Neuro-Psychopharmacology & Biological Psychiatry, 109, 110207, 2021)). Research regarding the COVID-19 outbreak addressed factors that contribute to anxiety people experienced as they tried to handle the changes in their lives associated with COVID-19 (Holmes et al. (The Lancet Psychiatry, 7(6), 547-560, 2020)). This paper focuses on diagnosis uncertainty as a particular source of anxiety. We use self-reported anxiety measures to understand how different stressors, and particularly how being sick or being unsure if one or one's close friends or relatives are sick, relate to overall anxiety levels. Five-hundred and thirty-three participants from a country with a stringent COVID-19 testing policy were surveyed in the spring of 2020 on various aspects of their anxiety and risk for depression, as well as on whether they or their friends or family had COVID-19. Analysis of survey results found that anxiety related to uncertainty regarding whether the survey responder or their friends or family were carrying COVID-19 may be even greater than fear of the virus itself. This paper discusses directional issues related to this finding and offers policy implications for decreasing anxiety during pandemics for certain types of communities. In addition to the main findings regarding diagnosis uncertainty and anxiety, this paper's results also indicate the importance of providing participants with an option for "not sure" in closed questions and imply the increased knowledge that can be gained by analyzing an unsure response independently of "yes" or "no".


Vascular endothelial growth receptor 1 acts as a stress-associated protein in the therapeutic response to thalidomide.
Thalidomide (THD) exhibits antitumor effects in several types of cancer. However, the failure of THD to inhibit tumor growth has also been observed in a number of murine models in vivo. The mechanism involved in the therapeutic failure of THD remains unclear. The present study demonstrated that, accompanied by growth-arresting and apoptosis-inducing effects (P<0.05), THD upregulated vascular endothelial growth factor receptor 1 (VEGFR1) expression levels in CT26 murine colorectal carcinoma cell lines. This in vitro phenomenon was also observed in various other cell lines, including human umbilical vein endothelial cells, SW480, SW620 and HCT116. Reactive oxygen species (ROS) levels were increased compared with those in the untreated control when cells were exposed to THD (P<0.05). Furthermore, results suggested that ROS suppression may have provoked the induction of VEGFR1 expression to some extent. In addition, the results revealed that THD failed to inhibit CT26 tumor growth in vivo and the expression of VEGFR1 protein was elevated by THD treatment compared with the control group in the murine colorectal tumor model (P<0.05). The results of further experiments suggested that VEGFR1 was elevated in response to various stress-associated situations, including chemotherapy, radiotherapy and thermotherapy, which indicate that it may act as a stress-associated protein. The present findings provide a foundation for the future study of VEGFR1-targeted therapy to enhance the efficacy of current therapies.


Mitochondrial micro-calpain is not involved in the processing of apoptosis-inducing factor.
Caspase-independent cell death, an important death pathway in many cells including neurons, is executed via apoptosis-inducing factor (AIF), an oxidoreductase, localized to the mitochondrial intermembrane space. AIF is processed and released from mitochondria following mitochondrial permeability transition pore (mPTP) formation, and translocates to the nucleus to induce DNA fragmentation and cell death. The release of AIF requires cleavage of its N-terminus anchored in the inner mitochondrial membrane. The protease responsible for this AIF truncation has not been established, although there is considerable evidence suggesting a role for micro-calpain. We previously found that a pool of micro-calpain is localized to the mitochondrial intermembrane space, the submitochondrial compartment in which AIF truncation occurs. The close submitochondrial proximity of mitochondrial micro-calpain and AIF gives support to the hypothesis that mitochondrial micro-calpain may be the protease responsible for processing AIF prior to its release. In the present study, AIF was released from rat liver mitochondria following mPTP induction by atractyloside. This release was inhibited by the cysteine protease inhibitor MDL28170, but not by more specific calpain inhibitors PD150606 and calpastatin. Atractyloside caused swelling in rat brain mitochondria, but did not induce AIF release. In a mitochondrial fraction from SH-SY5Y neuroblastoma cells, incubation with 5 mM Ca(2+) resulted in the activation of micro-calpain but not in AIF truncation. In summary, the localization of micro-calpain to the mitochondrial intermembrane space is suggestive of its possible involvement in AIF processing, but direct experimental evidence supporting such a role has been elusive.


Redox signaling of angiogenesis.
Reactive oxygen species (ROS) play a crucial role in vascular angiogenesis. Both in vitro and in vivo studies indicate that angiogenic response in vascular tissue is triggered by ROS signaling in a highly coordinated manner. It appears that massive amounts of ROS produced during ischemia and reperfusion in the vascular tissue, especially in heart, cause significant injury to the cardiomyocyte and endothelial cells. However, during the reperfusion, the same ROS potentiates a repair process and triggers a signal transduction cascade leading to angiogenesis. Although several other factors are likely to be involved for such angiogenic response, ROS certainly plays a crucial role as evident from its direct role as mediator of angiogenesis and inhibition of angiogenesis with free radical scavengers and/or antioxidants. Angiogenesis is regulated by redox-sensing transcription factors such as nuclear factor-kappaB, and oxidants such as hydrogen peroxide and free radicals, such as nitric oxide may function as second messengers in this highly coordinated process. Furthermore, expression of many angiogenic genes including those for vascular endothelial growth factor, fibroblast growth factor, platelet-derived growth factor, and receptors such as Flt-1, Flk-1, Ang-1, and Ang-2 are likely to be regulated by redox signaling. It is tempting to speculate that the angiogenic response is under the autocrine and/or paracrine control of one or more cytokines, which in turn is redox-regulated. Through angiogenesis, ROS appear to pave the way of repairing the vascular tissues that have been damaged during ischemia and reperfusion.


HDL Cholesterol Efflux Does Not Predict Cardiovascular Risk in Hemodialysis Patients.
The cardioprotective effect of HDL is thought to be largely determined by its cholesterol efflux capacity, which was shown to inversely correlate with atherosclerotic cardiovascular disease in populations with normal kidney function. Patients with ESRD suffer an exceptionally high cardiovascular risk not fully explained by traditional risk factors. Here, in a post hoc analysis in 1147 patients with type 2 diabetes mellitus on hemodialysis who participated in the German Diabetes Dialysis Study (4D Study), we investigated whether the HDL cholesterol efflux capacity is predictive for cardiovascular risk. Efflux capacity was quantified by incubating human macrophage foam cells with apoB-depleted serum. During a median follow-up of 4.1 years, 423 patients reached the combined primary end point (composite of cardiac death, nonfatal myocardial infarction, and stroke), 410 patients experienced cardiac events, and 561 patients died. Notably, in Cox regression analyses, we found no association of efflux capacity with the combined primary end point (hazard ratio [HR], 0.96; 95% confidence interval [95% CI], 0.88 to 1.06; P=0.42), cardiac events (HR, 0.92; 95% CI, 0.83 to 1.02; P=0.11), or all-cause mortality (HR, 0.96; 95% CI, 0.88 to 1.05; P=0.39). In conclusion, HDL cholesterol efflux capacity is not a prognostic cardiovascular risk marker in this cohort of patients with diabetes on hemodialysis.


Conventional cold excision combined with dermabrasion for rhinophyma.
A 65-year-old man, farmer by occupation, presented with redness and gradual enlargement of the nose. Examination revealed marked nodular enlargement of the nose and loss of normal nasal contours. Sebaceous material could be expressed from widened pores. The patient was diagnosed as rhinophyma of moderate degree. He was treated with cold knife excision combined with dermabrasion. A literature scan revealed that currently there is no evidence of superiority of much popular laser surgery over conventional cold knife surgery combined with dermabrasion for rhinophyma. Conventional surgery is time-tested, and it does not require expensive equipment or special training.


Self-Assembly of Electron Donor-Acceptor-Based Carbazole Derivatives: Novel Fluorescent Organic Nanoprobes for Both One- and Two-Photon Cellular Imaging.
In this study, we report fluorescent organic nanoprobes with intense blue, green, and orange-red emissions prepared by self-assembling three carbazole derivatives into nanorods/nanoparticles. The three compounds consist of two or four electron-donating carbazole groups linked to a central dicyanobenzene electron acceptor. Steric hindrance from the carbazole groups leads to noncoplanar 3D molecular structures favorable to fluorescence in the solid state, while the donor-acceptor structures endow the molecules with good two-photon excited emission properties. The fluorescent organic nanoprobes exhibit good water dispersibility, low cytotoxicity, superior resistance against photodegradation and photobleaching. Both one- and two-photon fluorescent imaging were shown in the A549 cell line. Two-photon fluorescence imaging with the fluorescent probes was demonstrated to be more effective in visualizing and distinguishing cellular details compared to conventional one-photon fluorescence imaging.


Gene expression profiling of the bone trabecula in patients with osteonecrosis of the femoral head by RNA sequencing.
Early diagnosis and treatment of osteonecrosis of the femoral head (ONFH) is challenging. Bone trabecula play a vital role in the severity and progression of ONFH. In the present study, the investigators used gene expression profiling of bone trabecula to investigate gene alterations in ONFH patients. Osteonecrotic bone trabecula (ONBT) such as necrosis, fibrosis, and lacuna were confirmed by histological examination in the patients. The adjacent 'normal' bone trabecula (ANBT) did not show any pathological changes. Gene sequencing data revealed that although ANBT showed no significant histological changes, alteration of mRNA profiling in ANBT was observed, similar to that in ONBT. Our results indicated that the alteration of mRNA profiling in ANBT may cause normal bone tissue to develop into necrotic bone. RNA-seq data indicated that 2,297 differentially abundant mRNAs were found in the ONBT group (1,032 upregulated and 1,265 downregulated) and 1,523 differentially abundant mRNAs in the ANBT group (744 upregulated and 799 downregulated) compared with the healthy control group. Gene ontology (GO) enrichment analysis suggested that fatty acid metabolism and degradation were the main zones enriched with differentially expressed genes (DEG). Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis indicated that peroxisome proliferator-activated receptor γ (PPAR-γ) pathway was the most significantly regulated pathway. Lipocalin-2 (LCN2), an osteoblast-enriched secreted protein, was significantly decreased in ONBT suggesting that downregulation of LCN2 might affect lipid metabolism and lead to hyperlipidemia, and thus promote pathogenesis of ONFH.


Nitric oxide regulates actin reorganization through cGMP and Ca(2+)/calmodulin in RAW 264.7 cells.
Nitric oxide (NO) has been reported to be involved in the regulation of pseudopodia formation, phagocytosis and adhesion in macrophages through the reorganization of actin. In the present study, we directly separated the globular (G) and filamentous (F) actin from quiescent or NO-stimulated macrophage-like cell line RAW 264.7 cells in order to investigate the dynamic redistribution of actin pools. We also focused on the regulatory mechanisms of actin assembly, induced by NO and its possible subsequent signaling pathway. We showed that predominant G-actin coexisted with Triton X-100-insoluble filamentous (TIF) and Triton X-100-soluble filamentous actin in resting RAW 264.7 cells. The exogenous NO produced by (+/-)-(E)-2-[(E)-hydroxyimino]-6-methoxy-4-methyl-5-nitro-3-hexenamide (NOR1), the endogenous NO induced by lipopolysaccharide (LPS) plus interferon-gamma (IFNgamma), and dibutyryl-cGMP increased the contents of TIF-actin in dose- and time-dependent manners and altered its morphology. The increase in the TIF-actin contents induced by NOR1 or LPS plus IFNgamma was efficiently blocked by the radical scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide and the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one or the arginine analogue N(G)-monomethyl-L-arginine acetate, respectively. Preincubation with the calmodulin antagonist W-7 almost completely blocked the NO-induced TIF-actin increase and morphological change. On the other hand, preincubation with C3 transferase, an inhibitor of Rho protein, efficiently prevented the change in cell morphology, but had no effect on the TIF-actin increase. We postulate that cGMP and subsequent Ca(2+)/calmodulin may be key regulators of actin reorganization in NO-stimulated RAW 264.7 cells.


Attitudes of women of childbearing age towards prenatal diagnosis in southeastern France.
The objective of this study was to explore women's attitudes towards prenatal diagnosis of trisomy 21 and to examine some of the factors possibly responsible for these attitudes before implementing in real practice serological screening of pregnant women at risk for trisomy 21. We carried out a telephone survey on a representative sample of women who had recently had a normal livebirth delivery in the Marseille district in 1990. The participation rate was 80 per cent and the average age of the mothers was 28.9 years. Among the 514 women interviewed, 78 per cent stated that they would ask for an amniocentesis for a 1 per cent risk of trisomy 21 at their next pregnancy. When adjusting for confounding factors, the decision to have or not to have an amniocentesis was found to depend not only on the women's attitude towards induced abortion, but also on their understanding of the risk involved and on the social context (knowing a handicapped child, discussion with the father). It also depended on the women's age and on what they knew about amniocentesis from the medical point of view. The risk of miscarriage can influence a woman's choice but this objection was not found to affect the women's decisions significantly in our survey. The data showed the existence of a high potential demand for fetal karyotyping.


Loss of heterozygosity is detected at chromosomes 1p35-36 (NB), 3p25 (VHL), 16p13 (TSC2/PKD1), and 17p13 (TP53) in microdissected apocrine carcinomas of the breast.
Apocrine carcinomas of the breast are an unusual special category of predominantly AR+, ER-, and PR- breast cancer, characterized by cells with abundant, eosinophilic cytoplasm and nuclei with often prominent nucleoli. To further investigate these lesions, loss of heterozygosity (LOH) was evaluated at multiple chromosomal loci, including loci frequently mutated in breast cancer. Twenty-five intraductal apocrine carcinomas, 11 invasive apocrine carcinomas, and six apocrine hyperplasias were retrieved from the files of the Armed Forces Institute of Pathology (Washington, DC) and Fairfax Hospital (Fairfax, VA). Cells from lesional as well as normal tissues were microdissected. LOH was performed at a number of chromosomal loci, including loci commonly altered in breast cancer: 1p35-36 (NB), 3p25.5 (VHL), 8p12 (D8S136), 9p21 (p16), 11p13 (D11S904), 11q13 (INT-2 and PYGM), 16p13.3 (TSC2/PKD1 gene region), 17p13 (TP53), 17q13 (NM23), and 22q12 (D22S683). Among informative in situ and invasive apocrine carcinomas, LOH was present in 33% of 15 cases for 17p13 (TP53), as well as 36% of 14 cases for 3p25 (VHL), 30% of 10 cases for 1p35-36 (NB), and 27% of 11 cases for 16p13.3 (TSC2/PKD1). A higher frequency of LOH was noted among invasive apocrine carcinomas (30 to 50%) compared with in situ apocrine carcinomas (23 to 33%) at these loci. LOH was present simultaneously for TP53 and either VHL or NB in five cases. Infrequent (< or =12%) or absent LOH was detected at the remaining loci, including several loci commonly mutated in breast cancer (i.e., INT2, PYGM, and NM23). LOH was not detected in any of the six apocrine hyperplasias. An intermediate frequency of allelic loss was detected at multiple tumor suppressor gene loci, including 17p13 (TP53), as well as 1p35-336 (NB), 3p25 (VHL), and 16p13 (PKD1/ TSC2), in apocrine carcinomas of the breast, with a higher overall frequency of LOH noted among invasive tumors compared with in situ tumors. Aside from LOH at p53, LOH was infrequent or absent at several other loci commonly mutated in breast cancer. This preliminary molecular evidence supports immunohistochemical data that apocrine carcinomas of the breast may possess unique mechanisms of carcinogenesis, compared with ordinary ductal carcinomas. However, further study is needed to support this assertion and to determine if the LOH detected is truly etiologic or if it is the result of genetic progression.


Aberrant DNA Methylation Mediates the Transgenerational Risk of Metabolic and Chronic Disease Due to Maternal Obesity and Overnutrition.
Maternal obesity is a rapidly evolving universal epidemic leading to acute and long-term medical and obstetric health issues, including increased maternal risks of gestational diabetes, hypertension and pre-eclampsia, and the future risks for offspring's predisposition to metabolic diseases. Epigenetic modification, in particular DNA methylation, represents a mechanism whereby environmental effects impact on the phenotypic expression of human disease. Maternal obesity or overnutrition contributes to the alterations in DNA methylation during early life which, through fetal programming, can predispose the offspring to many metabolic and chronic diseases, such as non-alcoholic fatty liver disease, obesity, diabetes, and chronic kidney disease. This review aims to summarize findings from human and animal studies, which support the role of maternal obesity in fetal programing and the potential benefit of altering DNA methylation to limit maternal obesity related disease in the offspring.


[Three-dimensional modelling of thoracic aortic aneurysm. A case report].
The anatomical forms of aneurysms are sometimes complex. Three-dimensional modelisation may be valuable in understanding the configuration and spatial orientation on one hand and also help in therapeutic decision making on the other. Two types of modelisation are reported with details of their methods and their respective values.


Antibiotic residue prevention methods, farm management, and occurrence of antibiotic residues in milk.
The objective of this study was to determine associations among the occurrence of antibiotic residues in bulk milk and various farm management practices. Ninety-four dairy farms were visited after antibiotic residues were detected in samples of their bulk milk (case farms) along with an equal number of residue-free farms (controls). Farmers completed questionnaires designed to elicit details of management practices used on farms and methods employed for prevention of antibiotic residues. Factors were initially examined unconditionally for statistical association with occurrence of residues; then multivariate associations were determined using multiple logistic regression. After adjusting for herd size in a logistic model, the risk of residues in milk was observed to increase in association with the frequent use of part-time labor in the milking of cows. The risk of residue occurrence was decreased in association with the use of milk residue test kits, when the farmer believed that increasing the dose of antibiotic required an increase in the withholding time of milk, and when tie stall and pipeline milking systems were used rather than milking parlors or tie stall and dumping station systems.


Testing Virulence of Different Species of Insect Associated Fungi against Yellow Mealworm (Coleoptera: Tenebrionidae) and Their Potential Growth Stimulation to Maize.
This paper investigates 71 isolates of two genera of entomopathogens, Metarhizium and Beauveria, and a biostimulative genus Trichoderma, for their ability to infect yellow mealworms (Tenebrio molitor) and to stimulate maize (Zea mays) growth. Fungal origin, host, and isolation methods were taken into account in virulence analysis as well. Isolates Metarhizium brunneum (1154) and Beauveria bassiana (2121) showed the highest mortality (100%) against T. molitor. High virulence seems to be associated with fungi isolated from wild adult mycosed insects, meadow habitats, and Lepidopteran hosts, but due to uneven sample distribution, we cannot draw firm conclusions. Trichoderma atroviride (2882) and Trichoderma gamsii (2883) increased shoot length, three Metarhizium robertsii isolates (2691, 2693, and 2688) increased root length and two M. robertsii isolates (2146 and 2794) increased plant dry weight. Considering both criteria, the isolate M. robertsii (2693) was the best as it caused the death of 73% T. molitor larvae and also significantly increased maize root length by 24.4%. The results warrant further studies with this isolate in a tri-trophic system.


The impact of concurrent and treated Ancylostoma ceylanicum hookworm infections on the immunogenicity of a recombinant hookworm vaccine in hamsters.
The effect of concurrent (active) and treated hookworm infections on the immunogenicity of vaccination with the recombinant fusion protein Ay-Ancylostoma-secreted protein 2 was analyzed in the Golden Syrian hamster. Hamsters were infected with the hookworm Ancylostoma ceylanicum and vaccinated with the recombinant protein, with Quil A used as adjuvant. As controls, hookworm-infected hamsters were treated with the anthelmintic drug pyrantel pamoate before vaccination. Naive hamsters (i.e., those with neither previous hookworm infections nor treatment) were also vaccinated. The proliferation capacities of carboxyfluorescein diacetate succinimidyl ester-positive lymphocytes from the hookworm-infected vaccinated group were reduced by 50% relative to the capacities of lymphocytes from uninfected or treated vaccinated hamsters; capacities were comparable to the rates observed in lymphocytes from the hamsters vaccinated with the adjuvant alone. Immunoglobulin G1 antibody responses were also reduced in the actively infected, untreated hamsters, and interferon- gamma and interleukin-4 cytokine mRNAs were down-regulated. Conversely, interleukin-10 and tumor necrosis factor- alpha mRNAs were up-regulated in those hamsters. These results suggest that hookworm infections have an immunomodulatory effect by impairing the immune response to an exogenous antigen during infection. The hookworm-associated immunodepression may have important implications for design of clinical trials of human vaccines and vaccination strategies.


Response of chickpea (Cicer arietinum L.) to terminal drought: leaf stomatal conductance, pod abscisic acid concentration, and seed set.
Flower and pod production and seed set of chickpea (Cicer arietinum L.) are sensitive to drought stress. A 2-fold range in seed yield was found among a large number of chickpea genotypes grown at three dryland field sites in south-western Australia. Leaf water potential, photosynthetic characteristics, and reproductive development of two chickpea genotypes with contrasting yields in the field were compared when subjected to terminal drought in 106kg containers of soil in a glasshouse. The terminal drought imposed from early podding reduced biomass, reproductive growth, harvest index, and seed yield of both genotypes. Terminal drought at least doubled the percentage of flower abortion, pod abscission, and number of empty pods. Pollen viability and germination decreased when the fraction of transpirable soil water (FTSW) decreased below 0.18 (82% of the plant-available soil water had been transpired); however, at least one pollen tube in each flower reached the ovary. The young pods which developed from flowers produced when the FTSW was 0.50 had viable embryos, but contained higher abscisic acid (ABA) concentrations than those of the well-watered plants; all pods ultimately aborted in the drought treatment. Cessation of seed set at the same soil water content at which stomata began to close and ABA increased strongly suggested a role for ABA signalling in the failure to set seed either directly through abscission of developing pods or seeds or indirectly through the reduction of photosynthesis and assimilate supply to the seeds.


Traumatic nasal injuries in general practice.
Traumatic nasal injuries are common in all age groups of the community. Significant nasal trauma can cause nasal fractures and a range of complicating injuries. This article provides general practitioners (GPs) with a succinct overview of pathology arising from nasal trauma, and a framework on the assessment and management of common nasal injuries. During assessment of traumatic nasal injuries, it is essential to exclude a septal haematoma, which requires urgent drainage. Undisplaced nasal fractures without functional symptoms can be managed conservatively. Displaced fractures should be referred for reduction. There is a window of two weeks before the displaced nasal bones start uniting. Investigations are rarely indicated for traumatic nasal injuries. Blood tests, including full blood count and coagulation screening, may be indicated in severe epistaxis. X-rays are not helpful for the assessment of traumatic nasal injuries. Computed tomography (CT) scans are only indicated if there is a suspected orbital, maxillary, frontal or zygomatic fractures.


Anaerobic respiration using Fe(3+), S(0), and H(2) in the chemolithoautotrophic bacterium Acidithiobacillus ferrooxidans.
The chemolithoautotrophic bacterium Acidithiobacillus ferrooxidans has been known as an aerobe that respires on iron and sulfur. Here we show that the bacterium could chemolithoautotrophically grow not only on H(2)/O(2) under aerobic conditions but also on H(2)/Fe(3+), H(2)/S(0), or S(0)/Fe(3+) under anaerobic conditions. Anaerobic respiration using Fe(3+) or S(0) as an electron acceptor and H(2) or S(0) as an electron donor serves as a primary energy source of the bacterium. Anaerobic respiration based on reduction of Fe(3+) induced the bacterium to synthesize significant amounts of a c-type cytochrome that was purified as an acid-stable and soluble 28-kDa monomer. The purified cytochrome in the oxidized form was reduced in the presence of the crude extract, and the reduced cytochrome was reoxidized by Fe(3+). Respiration based on reduction of Fe(3+) coupled to oxidation of a c-type cytochrome may be involved in the primary mechanism of energy production in the bacterium on anaerobic iron respiration.


Proteins implicated in sperm capacitation.
Spermatozoa after being deposited in the female reproductive tract spend a considerable time in this foreign environment prior to fertilization of the oocyte. Chang and Austin independently observed1,2 that this time spent by the spermatozoa in the female tract is not consequential but a necessary event in the life cycle of the male gamete, and Austin2 first called this maturation period of spermatozoa as 'Capacitation'. Ever since, attempts have been made to understand and unravel the molecular mechanism of capacitation. Based on the results obtained so far, it is clear that capacitation is guided by novel signal transduction pathways influencing varied aspects of spermatozoa. Capacitation could be, thus, defined as the cumulative molecular, cellular and physiological changes that occur in spermatozoa in the female reproductive tract to achieve the final competence to fertilize the oocyte. This review is structured so as to first understand the key features of capacitation and then to survey the players which bring about these changes during capacitation.


Substrate-Dependent Two-State Reactivity in Iron-Catalyzed Alkene [2+2] Cycloaddition Reactions.
Iron-catalyzed alkene [2+2] cycloaddition reactions represent a promising stepwise pathway to effect the kinetically hindered concerted [2+2] cycloaddition. However, the fundamental reactivity paradigm of these reactions remains unclear. Based on high level combined CASPT2/DFT modelings, herein we reveal an unprecedented substrate-dependent two-state reactivity scenario for the key C-C coupling in this iron catalysis, in which the representative substrates of mono-olefins only and mono-olefin plus 1,3-diene exhibit different reactivity paradigms. The role of the redox-active ligand is found to generate a ferric oxidation state for the metallacyclic intermediate of C-C coupling, thereby rendering a thermodynamically more accessible FeIII/FeI reductive elimination process compared with the otherwise FeII/Fe0 one. The enhancement of the spin state transition efficiency between the singlet and triplet states is predicted as an alternative way to increase the C-C coupling reactivity in the cross [2+2] cycloaddition reactions between mono-olefins and dienes. This work highlights the ab initio multi-reference method in describing very complicated open-shell iron catalysis.


Ling Zhi-8 mediates p53-dependent growth arrest of lung cancer cells proliferation via the ribosomal protein S7-MDM2-p53 pathway.
Ling Zhi-8 (LZ-8), an immunomodulatory protein, is derived from and has been cloned from the medicinal mushroom Ganoderma lucidum (Reishi or Ling Zhi); this protein exhibits immunomodulating and antitumor properties. We investigated the effects of recombinant LZ-8 protein (rLZ-8) on the proliferation of A549 human lung cancer cells. Here, we showed that rLZ-8 inhibits cell growth and that this is correlated with increased G(1) arrest. The treatment of A549 cells with rLZ-8 activated p53 and p21 expression, and both the G(1) arrest and the antigrowth effect were found to be p53 dependent. It was further demonstrated that rLZ-8 inhibited tumor growth in mice transplanted with Lewis lung carcinoma cells. Interestingly, rLZ-8 treatment was found to lead to nucleolar stress (or ribosomal stress) as evidenced by inhibition of precursor ribosomal RNA synthesis and reduced polysome formation in A549 cells. These changes resulted in an increasing binding of ribosomal protein S7 to MDM2 and a decreased interaction between MDM2 and p53. Taking these results together, we have identified a novel rLZ-8 antitumor function that positively modulates p53 via ribosomal stress and inhibits lung cancer cell growth in vitro and in vivo. Our current results suggest that rLZ-8 may have potential as a therapeutic intervention for the treatment of cancers that contain wild-type p53 and high expression of MDM2.


Desquamative interstitial pneumonitis complicating inflammatory bowel disease of childhood.
Sulfasalazine has been associated with bronchopulmonary complications of inflammatory bowel disease (IBD) in adults. We describe a 12-year-old boy who developed desquamative interstitial pneumonitis and hepatic cirrhosis several years following the onset of ulcerative colitis. The restrictive lung disease progressed despite cessation of sulfasalazine and initiation of corticosteroid therapy. We discuss a variety of bronchopulmonary complications of IBD and their association with sulfasalazine.


[Anterior cervical diskectomy and interbody arthrodesis using Cloward technique: retrospective study of complications and radiological results of 167 cases].
We performed a retrospective analysis of complications and radiological results in 167 patients surgically treated, for discal or spondylotic disease of the cervical spine, with Cloward procedure. Using uni and multivariate analysis, we tried to identify risk factors that might be correlated with surgical complications or radiological results. Surgical treatment was indicated for cervical radiculopathy in 68% of the patients and for myelopathy or radiculomyelopathy in the remaining 32%. The pathologic disease responsible of the symptomatology was soft disk herniation in 59% of the cases and spondylotic changes in 41%. The patients that underwent surgery because of myelopathy were one decade older, had a longer symptomatic period and presented multi-segmentary spondylotic disease with higher frequency than patients affected of radiculopathy. The most common segments operated were CS-C6 (44.3%) and C6-C7 (30.5%). Surgical mortality was 0.6% and morbidity 29.3%. Most of the complications were transient, although 4.8% of the patients developed permanent neurological deterioration. Complications were most commonly seen in the group of the patients undergoing surgery because of long-lasting myelopathy with multi-segmentary spondylotic disease, in those with vascular risk factors and in those operated of more than one segment. Surgeon anatomic knowledge and experience are critical for diminishing such complications. Non-union rate was 9.6%, and another 9.6% of the patients developed post-surgical kyphosis. Both factors correlated with the need of re-operation.


[Schopf-Schulz-Passarge syndrome: 2 cases].
Schöpf-Schulz-Passarge's syndrome is a rare autosomal recessive genodermatosis associating hypodontia, palmoplantar keratoderma, cysts of the eyelid margins, onychodysplasia and hypotrichosis. We report two new cases. Case no. 1: A 49 year-old woman complained of erosive and fissured palmoplantar keratoderma. Nails were fragile and dystrophic. Permanent teeth were absent. She also had many small cysts of the eyelid margins and a middle hypotrichosis. There was no consanguinity between her parents. Case no. 2: A 56 year-old man was seen for red, scaly and well marked palmoplantar keratoderma. Permanent teeth were absent. He had a hair loss since the age of 30. Nails were hypoplastic and there were many small cysts of the eyelids. Biopsy of one of the cysts showed a follicular cyst associated with sweat duct dystrophy. Schöpf-Schulz-Passarge's syndrome was diagnosed in these 2 patients. There was no evidence of associated cutaneous tumors. Differential diagnosis of Schöpf-Schulz-Passarge syndrome include other genodermatoses comprising palmoplantar keratoderma and dental abnormalities. Benign or malignant tumors are frequently associated: eccrine poromas, eccrine syringofibroadenomas, follicular tumors, basal cell and squamous cell carcinomas. Tumors usually appear after the age of 60. Regular follow-up and biopsy of the suspect lesions are necessary.


Comparative study of intubating conditions and hemodynamic changes during awake fiber-optic intubation using midazolam with fentanyl versus dexmedetomidine in cases of difficult airway.
The aim of the study is to compare intubating conditions and hemodynamic changes during awake fiber-optic intubation (AFOI) using midazolam and fentanyl versus dexmedetomidine in cases of difficult airway. A randomized prospective study was conducted in the department of oral and maxillofacial surgery, with a total of 60 patients, 18-55 years of age, ASA class I-II, of either sex with anticipated difficult airway planned for elective surgery. They were divided into two groups; group I patients received 1 μg/kg of dexmedetomidine and then an infusion of 0.5 to 0.7 μg/kg/hr of dexmedetomidine, whereas group II patients received 1 μg/kg of intra-venous (iv) fentanyl and 0.05 mg/kg of iv midazolam with additional doses of 0.02 mg/kg to achieve a Ramsay Sedation Scale score of ≥2. The ease of placement of the fiber-optic scope and the endotracheal tube and the patient's reaction to placement of the fiber-optic scope were assessed on a scale of 1-4 and were recorded as endoscopist satisfaction score and patient discomfort score, respectively. The endoscopy time ranged from 2.66 ± 1.00 (group I) to 3.90 ± 0.96 (group II) minutes and was found to be statistically significant (p < 0.05). Also, the patient discomfort score was recorded during endoscopy (1-4) and ranged from 1.3 ± 0.53 (group I) and 2.33 ± 0.66 (group II) and was found to be statistically significant (p value < 0.05). Patients undergoing the procedure who received dexmedetomidine were thus more comfortable than those who received fentanyl and midazolam combination. Dexmedetomidine provided better intubating conditions, patient tolerance, higher endoscopist satisfaction, and reduced hemodynamic responses compared to fentanyl and midazolam combinations. Also, the major advantage of dexmeditomidine for preservation of airway with a lesser degree of respiratory depression allows for safer use of AFOI in cases of difficult airway.


Single-lane 180 Gb/s DB-PAM-4-signal transmission over an 80 km DCF-free SSMF link.
We experimentally demonstrate the generation and successful transmission of a single-lane 180 Gb/s (90 GBd) duo-binary four-level pulse-amplitude modulation (DB-PAM-4) signal over an 80 km standard single-mode fiber with a net data-rate of 150 Gb/s, enabled by a dual-drive Mach-Zehnder modulator-aided dispersion pre-compensation. A net data rate of 168 Gb/s is also achievable, for ranges up to 40 km. To mitigate bandwidth limitations and error spreading, pre-coded DB-PAM-4 is used; the pre-coding provides a gain of approximately 1 dB. A Volterra filter and a maximum likelihood sequence estimator are used at the receiver side to reduce the linear and nonlinear distortions.


Evaluation of a novel monoclonal antibody mAb109 by immuno-PET/fluorescent imaging for noninvasive lung adenocarcinoma diagnosis.
Monoclonal antibodies are believed to be magic bullets and hold great potential for lots of biological process. About 100 μg of mAb109 was expressed in 5 × 106 cells after 10 days' immunization. 64Cu-NOTA-mAb109 was synthesized with the specific activity of 0.74 MBq/μg and high in vitro stability. The binding affinity of 64Cu-NOTA-mAb109 in A549 cells was determined to be 29.64 nM. 64Cu-NOTA-mAb109 displayed prominent tumor accumulation from 2 h to 60 h p.i. (9.34 ± 0.67 %ID/g). NIRF imaging of Cy5.5-mAb109 showed high accumulation till 9 days p.i., while tumors nearly can not be observed in negative groups, which was confirmed by autoradiography. Immunohistological study confirmed that mAb109 had strong and specific capacity to bind lung adenocarcinoma (concentration to 58 nM). Our study demonstrated mAb109 was a new platform for the development of novel agent for lung adenocarcinoma noninvasive imaging. The resulted 64Cu-NOTA-mAb109/Cy5.5-mAb109 show favorable imaging properties/specificity for A549 tumor and high sensitivity to human lung adenocarcinoma tissues.


Development of a risk prediction tool for patients with locally advanced and recurrent rectal cancer undergoing pelvic exenteration: protocol for a mixed-methods study.
Pelvic exenteration (PE) surgery represents the only potentially curative treatment option for patients with locally advanced or recurrent rectal cancer (LARRC). Given the potential morbidity, whether or not PE should be recommended for an individual patient presents a major decisional conflict. This study aims to identify the outcomes of PE for which there is consensus among patients, carers and clinicians regarding their importance in guiding treatment decision-making, and to develop a risk prediction tool which predicts these outcomes. This study will be conducted at a specialist PE centre, and employ a mixed-methods study design, divided into three distinct phases. In phase 1, outcomes of PE will be identified through a comprehensive systematic review of the literature (phase 1a), followed by exploration of the experiences of individuals who have undergone PE for LARRC and their carers (phase 1b, target sample size 10-20 patients and 5-10 carers). In phase 2, a survey of patients, their carers and clinicians will be conducted using Delphi methodology to explore consensus around the outcomes of highest priority and the level of influence each outcome should have on treatment decision-making. In phase 3 a, risk prediction tool will be developed using data from a single PE referral centre (estimated sample size 500 patients) to predict priority outcomes using multivariate modelling, and externally validated using data from an international PE collaboration. Ethical approval has been granted for phases 1 and 2 (X22-0422 and 2022/ETH02659) and for maintenance of the database used in phase 3 (X13-0283 and HREC/13/RPAH/504). Informed consent will be obtained from participants in phases 1b and 2; a waiver of consent for secondary use of data in phase 3 will be sought. Study results will be submitted for publication in international and/or national peer reviewed journals. CRD42022351909.


Mindfulness-Based Stress Reduction and Mindfulness-Based Cognitive Therapy for Depression: A Systematic Review of Cognitive Outcomes.
Summarize existing literature on cognitive outcomes of MBSR and MBCT for individuals with depression. Following PRISMA (2021) guidance, we conducted a systematic review. We searched databases for studies published from 2000 to 2020 which examined cognitive outcomes of MBSR and MBCT in individuals with at least mild depressive symptoms. The search result in 10 studies (11 articles) meeting inclusion criteria. We identified five single armed trials and five randomized controlled trials. Results indicated that three studies did not show any improvements on cognitive outcomes, and seven studies showed at least one improvement in cognitive outcomes. Overall, the review highlighted several inconsistencies in the literature including inconsistent use of terminology, disparate samples, and inconsistent use of methodology. These inconsistencies may help to explain the mixed results of MBSR and MBCT on cognitive outcomes. Recommendations include a more streamlined approach to studying cognitive outcomes in depressed individuals in the context of MBSR and MBCT.


Mutation of the rice gene PAIR3 results in lack of bivalent formation in meiosis.
Meiosis is essential for eukaryotic sexual reproduction and important for genetic diversity among individuals. Although a number of genes regulating homologous chromosome pairing and synapsis have been identified in the plant kingdom, their molecular basis remains poorly understood. In this study, we identified a novel gene, PAIR3 (HOMOLOGOUS PAIRING ABERRATION IN RICE MEIOSIS 3), required for homologous chromosome pairing and synapsis in rice. Two independent alleles, designated pair3-1 and pair3-2, were identified in our T-DNA insertional mutant library which could not form bivalents due to failure of homologous chromosome pairing and synapsis at diakinesis, resulting in sterility in both male and female gametes. Suppression of PAIR3 by RNAi produced similar results to the T-DNA insertion lines. PAIR3 encodes a protein that contains putative coiled-coil motifs, but does not have any close homologs in other organisms. PAIR3 is preferentially expressed in reproductive organs, especially in pollen mother cells and the ovule tissues during meiosis. Our results suggest that PAIR3 plays a crucial role in homologous chromosome pairing and synapsis in meiosis.


The association of hypertriglyceridemic waist phenotype with hypertension: A cross-sectional study in a Chinese middle aged-old population.
The present study aimed to evaluate the relationship between the hypertriglyceridemic waist (HTGW) phenotype and hypertension. We undertook a cross-sectional study with a sample of 9015 adults from China. The HTGW phenotype was defined as elevated waist circumference (WC) and elevated triglyceride (TG) concentration. Logistic regression analysis was used to evaluate the association between the HTGW phenotype and hypertension. The prevalence of hypertension was significantly higher in individuals with the HTGW phenotype, than in those with the normal waist normal triglyceride (NWNT) phenotype (89.9% vs 75.3%, respectively, P < .001). After adjusting for age, sex, BMI, current smoker, and current alcohol consumption, the HTGW phenotype was associated with hypertension (Odds Ratio (OR)1.53; 95% CI 1.25-1.87). After further adjustment for potential confounders, the HTGW phenotype was still significantly associated with hypertension (adjusted OR1.28; 95% CI 1.04-1.58) regardless of sex. The subgroup analyses generally revealed similar associations across all subgroups. This study indicated that the HTGW phenotype was strongly associated with hypertension, and blood pressure should be clinically monitored in individuals with the HTGW phenotype. We suggested a combined use of hypertriglyceridemia waist phenotype in identifying participants who are at high risk of hypertension.


Effect of adrenalectomy on the development of a pancreatic islet lesion in fa/fa rats.
Adrenalectomy prevents development of obesity and hyperinsulinaemia in obese (fa/fa) Zucker rats, thereby implicating the hypothalamo- pituitary-adrenal axis in the pathogenesis of obesity. In this study glucose-induced insulin secretion and glucokinase activity were investigated in isolated islets from adrenalectomized and control obese and lean female rats. Islets from control fa/fa rats were more sensitive to glucose with a half-maximal effective concentration (EC50) of 6.1 +/- 2.0 mmol. 1(-1) compared with 10.6 +/- 2.7 mmol. 1(-1) for adrenalectomized fa/fa rat islets. Adrenalectomy did not alter the islet sensitivity to glucose in the lean rats (EC50 of 9.4 +/- 1.5 mmol.1(-1) and 9.3 +/- 2.0 mmol. 1(-1) for adrenalectomized and control lean rats respectively). Mannoheptulose did not inhibit insulin secretion from control obese rats; however at concentrations of 1.0 mmol. 1(-1) or more it significantly inhibited glucose-induced insulin secretion in adrenalectomized obese and lean, and control lean rat islets (P < 0.05). In adrenalectomized fa/fa islets the glucokinase Km was increased twofold compared with the control fa/fa rats (9.5 +/- 1.5 mmol. 1(-1) vs 5.0 +/- 1.5 mmol. 1(-1), respectively), but there was no significant change in glucokinase Km in the lean rat islets after adrenalectomy. Mannoheptulose (10 mmol.1(-1) caused a significant reduction in glucose phosphorylation in disrupted islets of adrenalectomized fa/fa and lean, and of control lean rats, but not of control fa/fa rats. These data demonstrate that development of abnormal regulation of glycolysis in pancreatic islet beta cells of fa/fa rats, as indicated by the insulin response to manno-heptulose and glucokinase activity, is dependent on an intact hypothalamo-pituitary-adrenal axis.


Prevalence of mitral valve prolapse in panic disorder: effect of echocardiographic criteria.
Although several investigators have found a higher incidence of mitral valve prolapse (MVP) in patients with panic disorder (PD) and agoraphobia with panic attacks (AgP), there are now several conflicting reports. Discrepancy in the rate of echocardiographic diagnosis of MVP in PD/AgP may be due to different criteria used in evaluating the echocardiogram. In this study, 15 echocardiograms performed on patients with PD/AgP were evaluated by two separate expert echocardiographers. Each used his own standard criteria for diagnosing MVP. The first reader diagnosed MVP in 9 of 15 patients with PD/AgP while the second did not diagnose MVP in any of the 15 patients. This substantiates the belief that criteria variance strongly influences estimates of the prevalence of MVP among patients with PD/AgP.


The power of the force: mechano-physiology of the giant titin.
Titin - the largest protein in the human body - spans half of the muscle sarcomere from the Z-disk to the M-band through a single polypeptide chain. More than 30 000 amino acid residues coded from a single gene (TTN, in humans Q8WZ42) form a long filamentous protein organized in individual globular domains concatenated in tandem. Owing to its location and close interaction with the other muscle filaments, titin is considered the third filament of muscle, after the thick-myosin and the thin-actin filaments.


Microbiological Quality of Canadian Frozen Meat Pies.
One hundred and twenty samples of a variety of frozen meat pies were collected from 20 manufacturers across Canada and analyzed for aerobic colony count, coliforms, Salmonella , Clostridium perfringens , Staphylococcus aureus , and yeasts and molds. Salmonella was not isolated from any of the pies and only low numbers of C. perfringens and S. aureus were found. The highest aerobic colony count, coliforms and yeasts and molds were observed in pies with uncooked pastry. The degree of contamination in these pies was not alarmingly high to warrant establishment of microbiological standards or guidelines for these products.


Soy food intake behavior by socio-demographic characteristics of Korean housewives.
In this study, the soy food intake behaviors including perception and intake frequency of soybean foods by sociodemographic variables were analyzed in housewives. The perception of housewives for soy foods showed that soybean paste, soybean curd, and Dambuk were high in the descending order for nutritional quality and health promotion effect, and soybean paste received the highest score in taste and flavor. Soybean sprouts received the highest evaluation score in the economic aspect. In the aspect of safe food, soybean paste received the highest evaluation score, as mush as a traditional food. The analysis of perception by sociodemographic variables showed that soybean curd, Dambuk, and soybean sprouts had higher perceptions as education level increased, and soy milk had higher perceptions in subjects with younger age and with employment. In the intake frequency, more than 50% of the subjects had soybean curd, soybean sprouts, and soybean paste more than once a week. The analysis for correlation between the intake frequency of soy foods and the degree of perception showed that taste and flavor had high correlation with the intake frequency of soy foods except soybean sprouts. The intake frequency of soybean paste, Dambuk, and soy milk had positive correlations to familiarity and that of soy milk had positive correlations to nutrition and health perception, and those of soybeam paste, soybean sprouts, and soy milk had positive correlations to safe food perception. From the above results, housewives in Korea had very high perceptions to nutritional quality and health promotion effect of soy foods and the degree of perception and accompanied intake frequency had significant differences by age, education level, and economic level among sociodemographic variables.


Synthesis, Structure, and Properties of the Layered Oxide Chalcogenides Sr2CuO2Cu2S2 and Sr2CuO2Cu2Se2.
The structures of two new oxide chalcogenide phases, Sr2CuO2Cu2S2 and Sr2CuO2Cu2Se2, are reported, both of which contain infinite CuO2 planes containing Cu2+ and which have Cu+ ions in the sulfide or selenide layers. Powder neutron diffraction measurements show that Sr2CuO2Cu2Se2 exhibits long-range magnetic ordering with a magnetic structure based on antiferromagnetic interactions between nearest-neighbor Cu2+ ions, leading to a √2 a × √2 a × 2 c expansion of the nuclear cell. The ordered moment of 0.39(6) μB on the Cu2+ ions at 1.7 K is consistent with the value predicted by density functional theory calculations. The compounds are structurally related to the cuprate superconductors and may also be considered as analogues of the parent phases of this class of superconductor such as Sr2CuO2Cl2 or La2CuO4. In the present case, however, the top of the chalcogenide-based valence band is very close to the vacant Cu2+ 3d states of the conduction band, leading to relatively high measured conductivity.


Effects of Extended Viewing Distance on Accommodative Response and Pupil Size of Myopic Adults by Using a Double-Mirror System.
Purposes: This study discussed the accommodative response and pupil size of myopic adults using a double-mirror system (DMS). The viewing distance could be extended to 2.285 m by using a DMS, which resulted in a reduction and increase in the accommodative response and pupil size, respectively. By using a DMS, the reduction of the accommodative response could improve eye fatigue with near work. Method: Sixty subjects aged between 18 and 22 years old were recruited in this study, and the average age was 20.67 ± 1.09. There were two main steps in the experimental process. In the first step, we examined the subjects' refraction state and visual function, and then fitted disposable contact lenses with a corresponding refractive error. In the second step, the subjects gazed at an object from a viewing distance of 0.4 m and at a virtual image through a DMS, respectively, and the accommodative response and pupil size were measured using an open field autorefractor. Results: When the subjects gazed at the object from a distance of 0.4 m, or gazed at the virtual image through a DMS, the mean value of the accommodative response was 1.74 ± 0.43 or 0.16 ± 0.47 D, and the pupil size was 3.98 ± 0.06 mm or 4.18 ± 0.58 mm, respectively. With an increase in the viewing distance from 0.4 m to 2.285 m, the accommodative response and pupil size were significantly reduced about 1.58 D and enlarged about 0.2 mm, respectively. For three asterisk targets of different sizes (1 cm × 1 cm, 2 cm × 2 cm, and 3 cm × 3 cm), the mean accommodative response and pupil size through the DMS was 0.19 ± 0.16, 0.27 ± 0.24, 0.26 ± 0.19 D; and 4.20 ± 1.02, 3.94 ± 0.73, 4.21 ± 0.57 mm, respectively. The changes of the accommodative response and pupil size were not significant with the size of the targets (p > 0.05). In the low or high myopia group, the accommodative response of 0.4 m and 2.285 m was 1.68 ± 0.42 D and 0.21 ± 0.48 D; and 1.88 ± 0.25 D and 0.05 ± 0.40 D, respectively. The accommodative response was significantly reduced by 1.47 D and 1.83 D for these two groups. The accommodative microfluctuations (AMFs) were stable when a DMS was used; on the contrary, the AMFs were unstable at a viewing distance of 0.4 m. Conclusions: In this study, the imaging through a DMS extended the viewing distance and enlarged the image, and resulted in a reduction in the accommodative response and an increase in the pupil size. For the low myopia group and the high myopia group, the accommodative response and pupil size were statistically significantly different before and after the use of the DMS. The reduction of the accommodative response could be applied for the improvement of asthenopia.


Measuring Carbon-based Contaminant Mineralization Using Combined CO2 Flux and Radiocarbon Analyses.
A method is described which uses the absence of radiocarbon in industrial chemicals and fuels made from petroleum feedstocks which frequently contaminate the environment. This radiocarbon signal - or rather the absence of signal - is evenly distributed throughout a contaminant source pool (unlike an added tracer) and is not impacted by biological, chemical or physical processes (e.g., the 14C radioactive decay rate is immutable). If the fossil-derived contaminant is fully degraded to CO2, a harmless end-product, that CO2 will contain no radiocarbon. CO2 derived from natural organic matter (NOM) degradation will reflect the NOM radiocarbon content (usually <30,000 years old). Given a known radiocarbon content for NOM (a site background), a two end-member mixing model can be used to determine the CO2 derived from a fossil source in a given soil gas or groundwater sample. Coupling the percent CO2 derived from the contaminant with the CO2 respiration rate provides an estimate for the total amount of contaminant degraded per unit time. Finally, determining a zone of influence (ZOI) representing the volume from which site CO2 is collected allows determining the contaminant degradation per unit time and volume. Along with estimates for total contaminant mass, this can ultimately be used to calculate time-to-remediate or otherwise used by site managers for decision-making.


[The influence of cell surface hydrophobicity Candida sp. on biofilm formation on different biomaterials].
The ability of yeasts to form biofilm is believed to play an important role in patomechanism of fungal infection. Candida sp. is considered to form biofilm on surfaces of biomaterials used in production of catheters, drains and prosthesis. Therefore this may lead to serious problems in patients with biomaterials used for diagnostic or therapeutic purposes. The aim of the study was to evaluate the influence of cell surface hydrophobicity (CSH) of Candida sp. on biofilm formation on different biomaterials. CSH was evaluated by two methods: Salt Aggregation Test (SAT) and Microbe Adhesion to Hydrocarbon Test (MATH). Biofilm formation on different biomaterials was measured by Richard's method after 72 hour incubation at 37 degrees C. Candida biofilm formation occurred more frequently in case of strains exhibiting hydrophobic than hydrophilic properties of cell surface. The statistically significant correlation between CSH and ability of biofilm formation on different biomaterials was observed (p < 0.05).


Vortex stabilized flashlamps for dye laser pumping.
A unique vortex gas flow stabilized flashlamp has been developed for dye laser pumping. With a 2-musec current pulse the flashlamp can be operated at up to 250 J/pulse and can be run at a pulse repetition rate of up to 20 pulses/sec. At 200 J/pulse the useful lamp lifetime is several hundred thousand shots. Used for pumping the rhodamine 6G dye laser, the lamp has produced a 10-W average dye laser output.


KAI1/CD82 and MRP1/CD9 serve as markers of infiltration, metastasis, and prognosis in laryngeal squamous cell carcinomas.
The current study explored the expression of KAI1/CD82 and MRP1/CD9 and its significance in laryngeal squamous cell carcinoma (LSCC). The expression levels of KAI1/CD82 and MRP1/CD9 in 100 LSCC tissue specimens, as well as in 30 para-LSCC non-carcinomatous tissue specimens randomly taken from the patients, were assessed using the quantitative polymerase chain reaction (Q-PCR) and immunohistochemistry and correlations with pathological parameters of LSCC and their influence on survival function were analyzed. KAI1/CD82 and MRP1/CD9 showed basically consistent changes in both mRNA and protein expression. Their expression in the 30 LSCC specimens was significantly lower compared with that in the corresponding non-carcinous tissues (P < 0.01 or 0.05), notably correlating with TNM stage, differentiation degree, clinical stage, and lymphatic metastasis (P < 0.01 or 0.05), but not gender, age, and LSCC growth sites (P > 0.05). The median survival of patients with positive KAI1/CD82 and MRP1/CD9 protein expression was longer than that of patients with negative protein expression (P < 0.01 or 0.05). KAI1/CD82 protein expression negatively correlated with MRP1/CD9 protein expression in LSCC (χ(2) = 31.25, P < 0.01). KAI1/CD82 and MRP1/CD9 may jointly participate in the development of LSCC. They may serve as the markers for judging the infiltration, metastasis, and prognosis of LSCC.


Antioxidant response of soybean seedlings to joint stress of lanthanum and acid rain.
Excess of rare earth elements in soil can be a serious environmental stress on plants, in particular when acid rain coexists. To understand how such a stress affects plants, we studied antioxidant response of soybean leaves and roots exposed to lanthanum (0.06, 0.18, and 0.85 mmol L(-1)) under acid rain conditions (pH 4.5 and 3.0). We found that low concentration of La3+ (0.06 mmol L(-1)) did not affect the activity of antioxidant enzymes (catalase and peroxidase) whereas high concentration of La3+ (≥0.18 mmol L(-1)) did. Compared to treatment with acid rain (pH 4.5 and pH 3.0) or La3+ alone, joint stress of La3+ and acid rain affected more severely the activity of catalase and peroxidase, and induced more H2O2 accumulation and lipid peroxidation. When treated with high level of La3+ (0.85 mmol L(-1)) alone or with acid rain (pH 4.5 and 3.0), roots were more affected than leaves regarding the inhibition of antioxidant enzymes, physiological function, and growth. The severity of oxidative damage and inhibition of growth caused by the joint stress associated positively with La3+ concentration and soil acidity. These results will help us understand plant response to joint stress, recognize the adverse environmental impact of rare earth elements in acidic soil, and develop measures to eliminate damage caused by such joint stress.


Non-parametric Vignetting Correction for Sparse Spatial Transcriptomics Images.
Spatial transcriptomics techniques such as STARmap [15] enable the subcellular detection of RNA transcripts within complex tissue sections. The data from these techniques are impacted by optical microscopy limitations, such as shading or vignetting effects from uneven illumination during image capture. Downstream analysis of these sparse spatially resolved transcripts is dependent upon the correction of these artefacts. This paper introduces a novel non-parametric vignetting correction tool for spatial transcriptomic images, which estimates the illumination field and background using an efficient iterative sliced histogram normalization routine. We show that our method outperforms the state-of-the-art shading correction techniques both in terms of illumination and background field estimation and requires fewer input images to perform the estimation adequately. We further demonstrate an important downstream application of our technique, showing that spatial transcriptomic volumes corrected by our method yield a higher and more uniform gene expression spot-calling in the rodent hippocampus. Python code and a demo file to reproduce our results are provided in the supplementary material and at this github page: https://github.com/BoveyRao/Non-parametric-vc-for-sparse-st.


Evolution of clinical practice guidelines: evidence supporting expanded use of medicines.
Previous studies have shown that the primary factor underlying increased spending on pharmaceuticals has been the rising utilization of medications, rather than increases in unit drug price. This study examined the evolution of clinical practice guidelines to assess possible reasons for the rising drug volume. Clinical practice guidelines from 1970 to the present were reviewed for the six most prevalent treatable medical conditions/risk factors listed as priority areas by the Institute of Medicine. We searched the National Guidelines Clearinghouse, PubMed and Medline databases, and Web sites of relevant national organizations for US clinical practice guidelines published through January 2005. Information pertaining to the therapeutic regimen (eg, the frequency and duration of recommended treatment, when treatment should be initiated, the patient population for whom the guideline was intended) was abstracted and entered into evidence tables. Changes in guidelines were distributed across three themes that recommended evidence-based increases in medication use, including: (1) changes in the size of the treatable population; (2) changes in the number and type of recommended pharmaceutical therapeutic options, including movement from monotherapy to combination therapy, treatment of comorbidities, and use of newer types of medicines; and (3) changes in the therapeutic regimen, including a shift from episodic care to preventive and chronic care. Many of these changes point to an important, but not often noticed, addition of secondary prevention of disease effects to the objectives of medical care. These trends are likely to continue with important economic, clinical, and policy ramifications.


Expression of protein kinase C isoforms in cardiac hypertrophy and heart failure due to volume overload.
The present study determined whether changes in the activity and isoforms of protein kinase C (PKC) are associated with cardiac hypertrophy and heart failure owing to volume overload induced by aortocaval shunt (AVS) in rats. A significant increase in Ca2+-dependent and Ca2+-independent PKC activities in the homogenate and particulate fractions, unlike the cystolic fraction, of the hypertrophied left ventricle (LV) were evident at 2 and 4 weeks after inducing the AVS. This increase coincided with increases in PKC-alpha and PKC-zeta contents at 2 week and increases in PKC-alpha, PKC-beta1, PKC-beta2, and PKC-zeta contents at 4 weeks in the hypertrophied LV. By 8 and 16 weeks of AVS, PKC activity and content were unchanged in the failing LV. On the other hand, no increase in the PKC activity or isoform content in the hypertrophied right ventricle (RV) was observed during the 16 weeks of AVS. The content of G alpha q was increased in the LV at 2 weeks but then decreased at 16 weeks, whereas G alpha q content was increased in RV at 2 and 4 weeks. Our data suggest that an increase in PKC isoform content neither plays an important role during the development of cardiac hypertrophy nor participates in the phase leading to heart failure owing to volume overload.