Responses of Avena coleoptiles to suboptimal fusicoccin: kinetics and comparisons with indoleacetic Acid.
Proton excretion induced by optimal concentrations of indoleacetic acid (IAA) and fusicoccin (FC) differs not only in maximum rate of acidification but also in the lag before onset of H(+) excretion and in sensitivity to cycloheximide. Because these differences might simply be a consequence of the difference in rate of proton excretion, FC and IAA have now been compared using oat coleoptiles (cv. Victory) under conditions where the rates of acidification are more similar, i.e. suboptimal FC versus optimal IAA. As the concentration of FC is reduced, the rate of H(+) excretion decreases, the final equilibrium pH increases, and the lag before detectable acidification increases up to 7-fold. This enhanced lag period is not primarily a consequence of wall buffering, inasmuch as it persists when a low concentration of FC is added to sections which were already excreting H(+) in response to IAA. An extended lag also occurs, upon reduction of FC levels, in the hyperpolarization of the membrane potential, before enhancement of O(2) uptake and before the increased rate of Rb(+) uptake. The presence or absence of a lag is not a distinguishing feature between FC and IAA actions on H(+) excretion and cannot be used to discriminate between their sites of action. In contrast, the insensitivity of FC-induced H(+) excretion to cycloheximide, as compared with the nearly complete inhibition of this auxin effect by cycloheximide, persists even at dilute concentrations of FC. This seems to be a basic difference in H(+) excretion by IAA and FC.


Local regulation of epididymal anion secretion by pituitary adenylate cyclase-activating polypeptide.
The present study investigated the role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the regulation of electrogenic anion secretion by the rat cauda epididymal epithelium. PACAP38, which has been shown to affect secretory function in various exocrine and endocrine tissues, gave rise to a concentration-dependent increase in the short-circuit current (Isc). The PACAP38 effect was restricted to the apical aspect of the epididymal cells. The Isc response to PACAP38 was abolished in Cl-(-)free solution and completely inhibited by the Cl- channel blocker, diphenylamine-dicarboxylic acid. The Isc response to PACAP38 was also suppressed by pretreatment of the cells with the adenylate cyclase inhibitor, MDL12330A. The localization of PACAP38 was further investigated using an immunohistochemical technique. PACAP38 immunoreactivity was observed in the cauda epididymal tubules as well as in the cultured epithelium, indicating its epithelial origin. The present results suggest that Cl- secretion in the epididymis may be regulated by PACAP38, which could be locally synthesized and released by the epithelial cells, in a paracrine or autocrine fashion.


Efficacy of tracheal gas insufflation in acute respiratory distress syndrome with permissive hypercapnia.
This study was conducted to assess the CO2-elimination efficiency of tracheal gas insufflation (TGI) in 20 patients with acute respiratory distress syndrome and to compare its efficacy during volume-controlled (VCV) and pressure-controlled ventilation (PCV). TGI was initially applied as an adjunct to VCV, with continuous flows (Vcath) of 4 and 6 L/min delivered through a catheter positioned 2 cm above the carina. Total effective tidal volume (VTeff) was held constant. The percent reductions in PaCO2 (% delta PaCO2) were 13.3 +/- 2.1 and 16.7 +/- 2.7% at Vcath 4 and 6 L/min, respectively, which correlated well with the percent reduction in the end-tidal PCO2 from baseline (% delta PETCO2) (r = 0.75, p < 0.001). An inverse relationship (r = -0.65, p < 0.001 and r = -0.59, p < 0.01 at Vcath 4 and 6 L/min, respectively) was found between the % delta PaCO2 and the baseline ratio of artery to PETCO2 difference to PaCO2, which was determined as the fraction of alveolar dead space (VDalv) relative to total alveolar ventilation. Twelve patients were subsequently switched to PCV combined with Vcath 6 L/min, which provided a % delta PaCO2 of 16.1 +/- 3.0% (p = NS versus 17.1 +/- 2.6% during VCV). These data suggest that in patients with ARDS the change in PETCO2 may be helpful in predicting the decrement in PaCO2 during TGI, and the existence of a high VDalv tends to limit its effectiveness. Further, the efficacy of TGI with VCV is equivalent to that with PCV.


2-D chromatography applied to the study of block copolymers synthesized by nitroxide-mediated controlled free-radical seeded emulsion polymerization.
2-D chromatography with gradient polymer elution chromatography in the first dimension was used to characterize a series of block copolymers prepared by nitroxide-mediated controlled free-radical seeded emulsion polymerization. The data provide a detailed picture of the different populations generated during the successive stages of the reaction. In particular, deviations from ideal conditions, such as an exothermic temperature spike, are obvious from the 2-D chromatogram, and its interpretation provides unique insight into the reaction mechanisms. Finally, atomic force microscopy images obtained on films cast from copolymer solutions evidence the relationship between polymer microstructure and film morphology.


MSC-Derived Exosomes-Based Therapy for Peripheral Nerve Injury: A Novel Therapeutic Strategy.
Although significant advances have been made in synthetic nerve conduits and surgical techniques, complete regeneration following peripheral nerve injury (PNI) remains far from optimized. The repair of PNI is a highly heterogeneous process involving changes in Schwann cell phenotypes, the activation of macrophages, and the reconstruction of the vascular network. At present, the efficacy of MSC-based therapeutic strategies for PNI can be attributed to paracrine secretion. Exosomes, as a product of paracrine secretion, are considered to be an important regulatory mediator. Furthermore, accumulating evidence has demonstrated that exosomes from mesenchymal stem cells (MSCs) can shuttle bioactive components (proteins, lipids, mRNA, miRNA, lncRNA, circRNA, and DNA) that participate in almost all of the abovementioned processes. Thus, MSC exosomes may represent a novel therapeutic tool for PNI. In this review, we discuss the current understanding of MSC exosomes related to peripheral nerve repair and provide insights for developing a cell-free MSC therapeutic strategy for PNI.


The Critical Peri-implant Buccal Bone Wall Thickness Revisited: An Experimental Study in the Beagle Dog.
There is a lack of knowledge concerning the critical buccal bone thickness required for securing favorable functional and esthetic outcomes, conditioned to the dimensional changes after implant placement. A preclinical study was therefore carried out to identify the critical buccal bone wall thickness for minimizing bone resorption during physiologic and pathologic bone remodeling. A randomized, two-arm in vivo study in healthy beagle dogs was carried out. The first group of dogs was sacrificed 8 weeks after implant placement for histomorphometric examination of postsurgical resorption of the buccal bone wall. The second group of dogs was monitored during three ligature-induced peri-implantitis episodes and a spontaneous progression episode. Morphometric and clinical variables were defined for the study of physiologic and pathologic buccal and lingual bone loss. Seventy-two implants were placed in healed mandibular ridges of 12 beagle dogs. Two groups were defined: 36 implants were placed in sites with a thin buccal bone wall (< 1.5 mm), and 36 were placed in sites with a thick buccal bone wall (≥ 1.5 mm). No implants failed during the study period. For the great majority of the histomorphometric parameters, a critical buccal bone wall thickness of at least 1.5 mm seemed to be essential for maintaining the buccal bone wall during physiologic and pathologic bone resorption. Suppuration (+) and mucosal recession (-) were more often associated with implants placed in sites with a thin buccal bone wall. A critical buccal bone wall thickness of 1.5 mm at implant placement is advised, since a thicker peri-implant buccal bone wall (> 1.5 mm) is exposed to significantly less physiologic and pathologic bone loss compared with a thinner buccal bone wall (< 1.5 mm).


COVID-19: Why Has the Mortality Rate Declined?
This article explains how the mortality rate of an illness such as Coronavirus Disease 2019 (COVID-19) is calculated as well as how the definition of what is a "case" has changed from the earliest days of the pandemic to now. Many factors were not known about The Sudden Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) which causes COVID-19 at the beginning of the pandemic because it is a novel human pathogen. One key factor that was not known in the earliest days of the pandemic was that many patients are either asymptomatic or have symptoms so mild that they may not seek medical attention and hence these patients would not be identified as a "case" if that term is defined as being sufficiently symptomatic to be seeking medical attention. Cases in the earliest days of the pandemic were defined as based on having symptoms (eg, fever, cough, respiratory distress) after ruling out other possible causes. Cases now are defined by tests confirming that the person is shedding the SARS-CoV-2 (ie, a laboratory vs. a symptomatic diagnosis). The mortality rate of this virus dropped as a function of this change. On the basis of the results of an unintended, naturalistic experiment on an expeditionary cruise in March of 2020, there was more than a 5-fold drop in the calculated mortality rate due to this definitional change in what constituted a case. This column explains this issue and discusses its implications for effectively dealing with the SARS-CoV-2 (or COVID-19) pandemic.


[Pollution of operating rooms with volatile and gas anesthetics. Methods of prevention].
Gaseous anaesthetic pollution in operating theatres has been known since as far back as 1924. Following Vaisman and Cohen's epidemiology studies, health organizations have been involved in this professional concern. Halogenated vapours and nitrous oxide anaesthetic pollution have been accused of doubling the abortion rate and of moderately increasing the number of congenital abnormalities in the offsprings of anaesthetists. The liver and nervous system are also likely targets for anaesthetic pollution. Animal or cell culture experimental studies concerning pathological consequences of exposure to nitrous oxide or halogenated vapours give conflicting results and are not conclusive. The pollution rate is measured by chromatography and spectrophotometry. 25 ppm nitrous oxide and 2 ppm halothane are the upper limits allowed for air contamination. Total intravenous anaesthesia, closed circuits, draining away expired gases can prevent such pollution, but these techniques do have drawbacks. Pollution prevention is rather simple, moderately expensive and comforting for operating room staff.


Intergenerational Effect of Early Life Exposure to Permethrin: Changes in Global DNA Methylation and in Nurr1 Gene Expression.
Environmental exposure to pesticides during the early stages of development represents an important risk factor for the onset of neurodegenerative diseases in adult age. Neonatal exposure to Permethrin (PERM), a member of the family of synthetic pyrethroids, can induce a Parkinson-like disease and cause some alterations in striatum of rats, involving both genetic and epigenetic pathways. Through gene expression analysis and global DNA methylation assessment in both PERM-treated parents and their untreated offspring, we investigated on the prospective intergenerational effect of this pesticide. Thirty-three percent of progeny presents the same Nurr1 alteration as rats exposed to permethrin in early life. A decrease in global genome-wide DNA methylation was measured in mothers exposed in early life to permethrin as well as in their offspring, whereas untreated rats have a hypermethylated genomic DNA. Further studies are however needed to elucidate the molecular mechanisms, but, despite this, an intergenerational PERM-induced damage on progenies has been identified for the first time.


Accuracy of inhomogeneity correction in photon radiotherapy from CT scans with different settings.
We report an investigation on the accuracy of inhomogeneity correction in photon radiotherapy from CT scans with different settings. Specifically, the dosimetric differences from different CT scan parameters (kV, mAs) to phantoms and from different Hounsfield unit versus electron density (HU-ED) curves to patients are investigated. The absolute dose per monitor units (dose/MU) is used to quantify the results. We found that only for high-density bones (cranium, femoral tube, etc) using small field 18 MV beams, the dose/MU is up to 2% higher for CT scans using 80 kV than for 130 kV at a depth just beyond the bone and is up to 1-1.5% higher for CT scans using 80 mAs than for 300 mAs. For low-density bones (such as femoral head) and lung, the difference is 1% or less with different kV or mAs settings. The dose/MU varies with different HU-ED curves by up to 2%. The HU-ED curve from the stochiometric calibration was found to be more accurate based on a real measurement. A simplified 4-point curve provides nearly the same accuracy as the stochiometric calibration and may be used as an alternative for routine clinical application.


Lycopene ameliorates atrazine-induced oxidative damage in adrenal cortex of male rats by activation of the Nrf2/HO-1 pathway.
Atrazine (ATZ) is one of the most commonly used herbicides contaminating plants, soil and water resources. Several strategies have been used to counteract ATZ toxicity. Here, we tested the hypothesis that lycopene could ameliorate ATZ-induced toxicity in the adrenal cortex. For this purpose, 35 adult male albino rats were randomized into five equal groups: untreated control, vehicle control (received 0.5 mL corn oil/day), lycopene (treated with lycopene dissolved in 0.5 mL corn oil, 10 mg/kg b.w./day), ATZ (received ATZ dissolved in 0.5 mL corn oil 300 mg/kg b.w./day), and ATZ + lycopene (treated with ATZ and lycopene at the same previously mentioned doses). All treatments were given by oral gavage for 4 weeks. We found that ATZ exposure significantly increased relative adrenal weight, plasma ACTH levels, and adrenal oxidative stress as manifested by elevated malondialdehyde levels, decreased reduced glutathione content and depressed antioxidant enzyme activities in adrenal cortex tissues with respect to control groups. Furthermore, the transcription of adrenal cortex nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), nuclear factor kappa B, and caspase-3 genes was increased significantly compared with the control groups. This was accompanied with DNA fragmentation and structural and ultrastructural changes in zona glomerulosa and zona fasiculata of the adrenal cortex. Notably, all these changes were partially ameliorated in rats treated concomitantly with ATZ and lycopene. Our results showed that lycopene exerts protective effects against ATZ-induced toxicity in rat adrenal cortex. These effects may be attributed to the antioxidative property of lycopene and its ability to activate the Nrf2/HO-1 pathway.


Pilot trial of ribavirin for the treatment of laryngeal papillomatosis.
The antiviral drug ribavirin was used as an adjunct to laser surgery for the treatment of patients with laryngeal papillomatosis (LP). An uncontrolled clinical trial for four patients with ribavirin treatment at a daily dose of 23 mg/kg was performed. Three adults received drug prior to laser surgery and continuing orally for 6 months. One infant was treated for 3 months. Two adults achieved complete remissions for at least 2 consecutive months, and both patients developed only minimal recurrent disease in 4 months of follow-up. The other adult and the child sustained a partial response and an increased interval between the required surgeries. Ribavirin caused only a mild, reversible reduction in hemoglobin and reticulocytosis. This preliminary trial shows that ribavirin may be an effective therapy in combination with surgery for LP in a larger controlled clinical trial.


SCID-repopulating cell activity of human cord blood-derived CD34- cells assured by intra-bone marrow injection.
Precise analysis of human CD34-negative (CD34(-)) hematopoietic stem cells (HSCs) has been hindered by the lack of a simple and reliable assay system of these rare cells. Here, we successfully identify human cord blood-derived CD34(-) severe combined immunodeficiency (SCID)- repopulating cells (SRCs) with extensive lymphoid and myeloid repopulating ability using the intra-bone marrow injection (IBMI) technique. Lineage-negative (Lin(-)) CD34(-) cells did not show SRC activity by conventional tail-vein injection, possibly due to their low levels of homing receptor expression and poor SDF-1/CXCR4- mediated homing abilities, while they clearly showed a high SRC activity by IBMI. They generated CD34(+) progenies not only in the injected left tibia but also in other bones following migration. Moreover, they showed slower differentiating and reconstituting kinetics than CD34(+) cells in vivo. These in vivo-generated CD34(+) cells showed a distinct SRC activity after secondary transplantation, clearly indicating the long-term human cell repopulating capacity of our identified CD34(-) SRCs in nonobese diabetic (NOD)/SCID mice. The unveiling of this novel class of primitive human CD34(-) SRCs by IBMI will provide a new concept of the hierarchy in the human HSC compartment and has important implications for clinical HSC transplantation as well as for basic research of HSC.


Outcomes of percutaneous nephrolithotomy in elderly versus young patients under regional anesthesia: A comparative study.
Surgical management of elderly patients with renal calculi is inherently challenging. We compared the efficacy and safety of percutaneous nephrolithotomy (PCNL) performed under regional anesthesia between elderly patients (age >65 years) and patients aged <65 years. Between July 2015 and June 2016, fifty patients aged >65 years with renal stones (size >1.5 cm) were treated with PCNL under regional anesthesia (elderly group). We retrospectively compared the outcomes with those obtained in an equal number of patients aged <65 years (younger group) who underwent PCNL under regional anesthesia. Patients with staghorn stones and pyonephrosis and falling under the American Society of Anesthesiologists (ASA) Grade IV were excluded. Data pertaining to demographic characteristics, body mass index, stone bulk, operative time, tract size, number of tracts required, blood loss, clearance rates, complications, and length of hospital stay were analyzed. The mean age at presentation in the elderly and younger groups was 66.8 ± 2.1 years and 38.7 ± 11 years, respectively; 56% of the patients in the elderly age group had ASA Grade II, whereas 58% in the younger age group had ASA Grade I. The mean stone size and the number of tracts were comparable in both the groups, whereas operative time was slightly longer in the elderly group (58.54 ± 18 vs. 51.98 ± 18 min; P < 0.05). Postoperative complications and stone-free rates (94% vs. 92%, respectively) were comparable in the two groups. Age itself should not deter the treatment of elderly patients with renal stones as PCNL under regional anesthesia is safe and effective in elderly patients; outcomes in elderly and younger patients were comparable in this study.


Interest in participating in smoking cessation treatment among Latino primary care patients.
Smoking is the leading preventable cause of disease and death for U.S. Latinos. This study identified correlates of interest in participating in a smoking cessation program among urban Latinos seen in community clinics. Interviews were completed with 141 current smokers. Participants were predominantly Spanish-speaking (93%) males (66%), who were on average 37.6 years old and smoked 8.7 cigarettes per day. Over two-thirds (63%) of participants were "definitely interested" in participating in a smoking cessation program. Participants who smoked more cigarettes per day and reported greater nicotine dependence, depression, and readiness to quit were more likely to be interested, while those employed fulltime were less likely to report high interest. Treatment preferences were consistent with Clinical Practice Guidelines recommending counseling, social support, and pharmacotherapy. Results support recommendations that healthcare providers intervene with all Latino smokers, including light smokers and those who do not report initial interest in smoking cessation.


Clinical significance of different atlas of intracavitary electrocardiogram for PICC localization in 961 cases.
To explore the application of ECG-guided localization technology in PICC catheterization and the clinical significance of different maps of intracavitary ECG in PICC tip localization. In the process of catheter placement under the guidance of ultrasound, the technique of intracavitary ECG location was used. The length of the catheter was measured on the body's surface. The amplitude of the P-wave and the QRS-wave groups of electrocardiograms before and during catheter placement was recorded. Nine hundred sixty-one patients who underwent X-ray chest film examination after catheterization were imaged on the chest film at the tip of the catheter. Eight hundred four cases had a characteristic P wave, 83.66%, of which, 331 cases (50% < P/R ≤80%) had 99.09%; 425 cases (80% < P/R ≤100%) had 99.29%; 48 cases (P/R >100%) had 100%. One hundred eighteen cases of non-specific P wave accounted for 12.28% and 79.66% of chest radiographs, of which 72 cases of P/R <50% were 100%; 46 cases of unchanged P wave were 47.83%; 34 cases of special cases accounted for 3.54% and 55.88% of chest radiographs; five cases of interference wave accounted for 0.25%, and the chest radiographs were self-control. The in-place rate of the body contrast catheter was 80%. The accuracy of the ECG characteristic map in guiding the location of the PICC tip is higher than that of the non-characteristic P wave, and it has more clinical significance in locating the best position of the PICC tip.


Inositol catabolism, a key pathway in sinorhizobium meliloti for competitive host nodulation.
The nitrogen-fixing symbiont of alfalfa, Sinorhizobium meliloti, is able to use myo-inositol as the sole carbon source. Putative inositol catabolism genes (iolA and iolRCDEB) have been identified in the S. meliloti genome based on their similarities with the Bacillus subtilis iol genes. In this study, functional mutational analysis revealed that the iolA and iolCDEB genes are required for growth not only with the myo-isomer but also for growth with scyllo- and d-chiro-inositol as the sole carbon source. An additional, hypothetical dehydrogenase of the IdhA/MocA/GFO family encoded by the smc01163 gene was found to be essential for growth with scyllo-inositol, whereas the idhA-encoded myo-inositol dehydrogenase was responsible for the oxidation of d-chiro-inositol. The putative regulatory iolR gene, located upstream of iolCDEB, encodes a repressor of the iol genes, negatively regulating the activity of the myo- and the scyllo-inositol dehydrogenases. Mutants with insertions in the iolA, smc01163, and individual iolRCDE genes could not compete against the wild type in a nodule occupancy assay on alfalfa plants. Thus, a functional inositol catabolic pathway and its proper regulation are important nutritional or signaling factors in the S. meliloti-alfalfa symbiosis.


Quantitative analysis of catalysis and inhibition at horseradish peroxidase monolayers immobilized on an electrode surface.
Out of several tries, biotinylation of the electrode surface by means of a sacrificial biotinylated immunoglobulin, followed by the anchoring of an avidin-enzyme conjugate appears as the best procedure for depositing a horseradish peroxidase (HRP) monolayer onto an electrode surface, allowing a high-yield immobilization of the enzyme within a stable and highly catalytic coating. Cyclic voltammetry is an efficient means for analyzing the catalytic reduction of H(2)O(2) at such HRP monolayer electrodes in the presence of [Os(III)(bpy)(2)pyCl](2+) (with bpy = bipyridine and py = pyridine) as a one-electron reversible cosubstrate. The odd shapes of current-potential responses, unusual bell-shaped variation of the peak or plateau current with the substrate concentration, hysteresis and trace crossing phenomena, and dependence or lack of dependence with the scan rate, can all be explained and quantitatively analyzed in the framework of the same catalysis/inhibition mechanism as previously demonstrated for homogeneous systems, taking substrate and cosubstrate mass transport of into account. According to H(2)O(2) concentration, limiting-behavior analyses based on the dominant factors or complete numerical simulation were used in the treatment of experimental data. The kinetic characteristics derived from these quantitative treatments implemented by the determination of the amount of enzyme deposited by the newly developed droplet depletion method allowed a comparison with homogeneous characteristics to be drawn. It shows that HRP remains nearly fully active once anchored on the electrode surface through the avidin-biotin linkage. On the basis of this full mechanistic and kinetic characterization, the analytical performances in H(2)O(2) detection and amperometric immunosensor applications are finally discussed.


[Ultrasound-guided percutaneous composite thermal ablation technique in treatment of medium and large hepatocellular carcinoma].
To evaluate the clinical values of ultrasound-guided percutaneous composite thermal ablation technique in the treatment of medium and large hepatocellular carcinoma (HCC). By the composite technique of multiple-needle insertion and multi-point energy application, ultrasound-guided percutaneous radiofrequency ablation (RFA) or microwave ablation (MWA) were employed to treat 68 patients of HCC with tumor nodule > or = 3.1 cm in diameter. There was a total number of 73 tumor nodules, with a mean diameter of (4.5 +/- 1.7) cm (3.1-13.0 cm). Sixty-three patients had single tumor nodule, and the remaining 5 had 2 nodules. With a follow-up time of 1.9 - 67.6 months [(16.0 +/- 14.8) months], the local and long-term efficacy was analyzed. Hepatic subcapsular hematoma were found in 1 patient. And skin burning in 1 patient 1. Complete ablation rate was 78.1% (57/73), local tumor progression was presented in 24.6% tumor nodules (14/57) and distant recurrence developed in 56.7% patients (38/67). The 1-, 3-, 5-years survival rate was 62.3%, 29.6% and 21.6%, respectively, with a median survival time of 18.6 months, (95% confidence interval: 10.9 months, 26.3 months). There were no remarkable differences in complete ablation rate, local tumor progression, distant recurrence rate and survival rate between RFA and MWA. By the composite ablation technique, ultrasound-guided percutaneous thermal ablation was effective in treating medium and large unresectable HCC. And the advantage is minimal invasiveness. RFA and MWA had no marked differences in terms of therapeutic efficacy.


Metabolism of low density lipoprotein by bovine endothelial cells as a function of cell density.
The amount of low density lipoprotein (LDL) bound to the LDL receptor of bovine aortic endothelial cells at widely varying cell densities was measured by two methods: the commonly used dextran-sulfate-release method after LDL binding at 0-4 degrees C, and the method of assay of the LDL internalized in 30 minutes at 37 degrees C after LDL binding at 0-4 degrees C. Values obtained for LDL binding by the two methods were similar. At cell densities ranging from very sparse (6 X 10(3) to very dense (greater than 10(6) cells/cm2), both binding and degradation of 125I-LDL decreased in a nonlinear but parallel manner as cell density increased. This change began to occur at subconfluent densities and appeared to be not simply the result of establishment of a confluent cell layer. Thus, endothelial cells respond to changes in cell density with reciprocal changes in LDL metabolism in the same manner as reported for fibroblasts, so that at confluency both LDL receptor activity and LDL degradation are very low.


Self help smoking cessation in pregnancy: cluster randomised controlled trial.
To evaluate the effectiveness of a self help approach to smoking cessation in pregnancy. Pragmatic cluster randomised controlled trial with community midwife as the unit of randomisation. Three NHS hospital trusts in England. 1527 women who smoked at the start of pregnancy. A series of five self help booklets comprising a step by step programme to increase motivation for quitting smoking and to teach strategies for cessation and relapse prevention. The first booklet was given to the women by a midwife at the earliest opportunity in antenatal care, together with a booklet for partners, family members, and friends. The remaining four booklets were mailed directly to the women. The primary outcome was smoking cessation validated by cotinine measurement at the end of the second trimester of pregnancy. Other outcomes were self reported smoking status and cigarette consumption among daily smokers. Qualitative data exploring the acceptability of the intervention and the way that smoking cessation advice was delivered in both trial arms were also collected. Smoking cessation rates were low: the cotinine validated rates were 18.8% (113/600) in the intervention group and 20.7% (144/695) in the normal care group (difference 1.9%, 95% confidence intervals -3.5% to 7.3%). Self reported quit rates were higher. In the intervention group, 156 (25.6%) women reported not smoking for at least seven days, compared with 207 (29.1%) in the normal care group. In both groups, median self reported daily cigarette consumption among daily smokers was 10 cigarettes per day. Pregnant women and midwives approved of the intervention, but the way in which it was delivered varied considerably. For the primary smoking outcome, the degree of clustering at the midwife level was non-trivial (intracluster correlation coefficient 0.031). The self help intervention was acceptable but ineffective when implemented during routine antenatal care. More intensive and complex interventions, appropriately targeted and tailored, need to be developed and evaluated. Validated smoking cessation rates among pregnant women are substantially lower than the self reported rates on which current smoking policy is based.


Capillary isoelectric focusing of physiologically derived proteins with on-line desalting of isotonic salt concentrations.
Capillary isoelectric focusing within capillaries (cIEF) is a powerful and practical method for high-resolution separation of components within complex biological mixtures. However, a major problem has always existed; separation performance is usually degraded by the presence of salts within the sample. Normally this requires the removal of these components by some off-line sample cleanup method, prior to analyte separation by cIEF. In this study, we have shown it is possible to efficiently remove high salt levels from samples by on-line voltage ramping of the applied CE voltage. To allow this technique to be used effectively, a customized version of an existing method to internally coat a fused-silica capillary has been developed and examined for interexperimental reproducibility. We describe the systematic examination of the desalting process and its optimization through the use of model protein systems. Furthermore, we demonstrate the automated application of this on-line desalting cIEF scheme to studies of whole human blood and human cerebrospinal fluid which have undergone no manipulation or work up prior to cIEF analysis.


Increased beta-adrenergic receptors in the light-density membrane fraction in lungs from senescent rats.
There is a dynamic balance between cell surface and intracellular beta-adrenergic receptors. To investigate whether this balance is altered with aging, we determined the number of beta-adrenergic receptors in the heavy- (48,000 x g) and light-density (200,000 x g) membrane fractions from lungs and hearts of 4-, 13-, and 25-month-old rats. There were no differences in the density of receptors with age in the heavy membrane fraction. However, the density of receptors in the light-density fraction from lungs increased with age (109 +/- 7, 230 +/- 43, and 225 +/- 36, F(2,12) = 4.4, p less than .05). Receptors in the heavy membrane fraction expressed both high and low affinity binding for isoproterenol, whereas receptors in light-density fraction expressed only low affinity binding. In contrast to the lung, there were no changes in the number of receptors with age in the light-density membrane fraction from hearts. These data indicate there are increased numbers of beta-adrenergic receptors in the light membrane fraction in lungs from aged rats, which are separated from the other components of the adenylate cyclase complex.


Deep Learning-Based Pan-Cancer Classification Model Reveals Tissue-of-Origin Specific Gene Expression Signatures.
Cancer tissue-of-origin specific biomarkers are needed for effective diagnosis, monitoring, and treatment of cancers. In this study, we analyzed transcriptomics data from 37 cancer types provided by The Cancer Genome Atlas (TCGA) to identify cancer tissue-of-origin specific gene expression signatures. We developed a deep neural network model to classify cancers based on gene expression data. The model achieved a predictive accuracy of >97% across cancer types indicating the presence of distinct cancer tissue-of-origin specific gene expression signatures. We interpreted the model using Shapley additive explanations to identify specific gene signatures that significantly contributed to cancer-type classification. We evaluated the model and the validity of gene signatures using an independent test data set from the International Cancer Genome Consortium. In conclusion, we present a robust neural network model for accurate classification of cancers based on gene expression data and also provide a list of gene signatures that are valuable for developing biomarker panels for determining cancer tissue-of-origin. These gene signatures serve as valuable biomarkers for determining tissue-of-origin for cancers of unknown primary.


[Responses to customer complaints at commercial laboratories].
For commercial laboratories, one of the routine duties involves responding to various kinds of inquiries and complaints received from customers. As causes of complaints, lack of communication between the laboratory and customer, and test errors were considered. In this paper, complaints received by our laboratory were collected and classified by content, and measures to prevent test error are reported. We think the complaints contain important information that can be used to improve the quality of our laboratory. We hope that reinforcement of communication with customers and promoting test knowledge among the customers can produce more clearly worded complaints which will provide more valuable information. We try to receive and deal with these complaints seriously.


The role of leukotrienes and eosinophil cationic protein in acute respiratory syncytial virus bronchiolitis.
The Respiratory Syncytial Virus (RSV) is the leading cause of lower respiratory tract infection in infants and by 2.5 to 3 years of age most children have been infected with approximately 1-2% of all infected infants requiring hospital admission. Both immunologic and nonimmunologic factors have been implicated in the susceptibility to symptomatic RSV-induced disease although most attention has been directed towards host responses and their role in the pathogenesis of the associated airway obstruction. Although the mechanisms and host responses associated with symptomatic RSV disease are not yet clear, products more usually associated with allergic inflammation such as cysteinyl leukotrienes and eosinophil cationic protein have been detected in airway secretions of affected infants. Leukotrienes are synthesized through the 5-lipoxygenase pathway from the arachidonic acid which is released from the phospholipids forming the membrane of activated cells. They are potent inflammatory mediators and can cause increased secretion of mucus, airway oedema, bronchoconstriction, airway obstruction. Eosinophil cationic protein is a unique protein from the noncore matrix of the eosinophil cells. Eosinophils and eosinophil mediators are involved in the process of airway obstruction found in many common paediatric pulmonary disorders. The potential role of leukotrienes and eosinophil cationic protein in RSV disease, especially bronchiolitis, are reviewed.


Fundamental changes to EPA's research enterprise: the path forward.
Environmental protection in the United States has reached a critical juncture. It has become clear that to address the complex and interrelated environmental challenges we face, we must augment our traditional approaches. The scientific community must build upon its deep understanding of risk assessment, risk management, and reductionism with tools, technologies, insights and approaches to pursue sustainability. The U.S. Environmental Protection Agency (EPA) has recognized this need for systemic change by implementing a new research paradigm called "The Path Forward." This paper outlines the principles of the Path Forward and the actions taken since 2010 to align EPA's research efforts with the goal of sustainability.


Liver Metastases From Breast Cancer: What Role for Surgery? Indications and Results.
Liver metastases from breast cancer (LMBC) have long been considered as a systemic disease because of the hematological route of dissemination, requiring noncurative management. In fact, despite recent advances in drug therapies personalized to tumor phenotype, the chances of a cure are nil and there is little hope of long-term survivors after nonsurgical management alone. By contrast, there is a growing evidence in the literature for satisfactory long-term results after a combination of chemotherapy and liver resection, with 5-year survival reaching >40% in some series. The surgical management of LMBC is still restricted to carefully selected patients, managed in high-volume hepatobiliary surgery and cancer research centers. Under these conditions, resection can be performed at the price of very limited morbidity and near zero mortality. The best results after the resection of LMBC are obtained after applying selection criteria based on small metastases (<4-5 cm), minor hepatectomy, radical resection (ideally R0, or R1), stable disease (ideally in regression) after neoadjuvant therapy, and a delay between primary and secondary lesions longer than 1 or 2 years (reflecting a favorable oncologic context). The age of the patient, her hormone receptor status, and HER2 overexpression are not strong predictors of survival. The role of radiological alternatives still needs to be defined (radiofrequency, microwave ablation, radioembolization), and these raise questions regarding a reliable pretreatment assessment of tumor spread. Finally, surgical results are based on scarce evidence and need to be confirmed by large-scale studies so that they will be more widely accepted by the medical community.


Preparation of carboplatin-Fe@C-loaded chitosan nanoparticles and study on hyperthermia combined with pharmacotherapy for liver cancer.
Magnetic fluid hyperthermia is a kind of technology for treating tumors based on nanotechnology. It is suitable to various types of tumors. The purpose of this study was to prepare carboplatin-Fe@C-loaded chitosan nanoparticles with Fe@C as a magnetic core and to investigate efficacy of hyperthermia combined with chemotherapy for transplanted liver cancer in rats. Fe@C nanopowder was treated with dilute hydrochloric acid to prepare Fe@C nanocage. Carboplatin-Fe@C-loaded chitosan nanoparticles were prepared by reverse microemulsion method with the nanocages as the magnetic cores, chitosan as the matrix. The shape, size, drug-loading rate, and in vitro cumulative release of the nanoparticles were observed and heat product under high frequency alternating electromagnetic field in vitro was explored. Eighty rats with transplanted liver cancer were randomly divided into 4 groups (group A: control group, group B: free carboplatin group, group C: nanoparticles with static magnetic field group, and group D: nanoparticles with static field and alternating magnetic field). Drug was injected into the hepatic artery. The therapeutic effect of hyperthermia combined with chemotherapy for tumor, toxicity and rat survival time were observed. Carboplatin-Fe@C-loaded chitosan nanoparticles were spherical in shape with an average size of (207 +/- 21) nm and high saturation magnetization. The drug-loading rate of the nanoparticles was 11.0 +/- 1.1%. The cumulative release percentage of carboplatin-Fe@C-loaded chitosan nanoparticles in vitro at different point time phase of 24 h, 48 h, 72 h, 96 h and 120 h were 51%, 68%, 80%, 87% and 91%, respectively. With an increase in carboplatin-Fe@C-loaded chitosan nanoparticle concentration and magnetic field strength, the heating rate and constant temperature of carboplatin-Fe@C-loaded chitosan nanoparticles dispersed in physiological saline were increased in an alternating magnetic field. In vivo experiments showed that after particle injection, tumor temperature reached 42.6 degrees +/- 0.2 degrees C within 10 min in the alternating magnetic field; and the temperatures in the right hepatic lobes and the rectum were significantly lower than in the tumor and the constant temperature could last up to 30 min. The inhibition ratio of tumor weight in group D was significantly enhanced, no obviously toxic and side-effect occurred and survival time was prolonged. Carboplatin-Fe@C-loaded chitosan nanoparticles possess good magnetic targeting and heat production properties. They can target liver cancer tissue by static magnetic field, and with the application of alternating magnetic field, effectively raise tumor tissue temperature and facilitate tumor apoptosis. The combination of chemotherapy and magnetic materials into nanoparticles as described herein demonstrates promising efficacy.


Int6 and Moe1 interact with Cdc48 to regulate ERAD and proper chromosome segregation.
Int6/eIF3e is implicated in tumorigenesis, but its molecular functions remain unclear. We have studied its fission yeast homolog Yin6, reporting that it regulates proteolysis by controlling the assembly/localization of proteasomes, and binds directly to another conserved protein, Moe1. In the present study, we isolated Cdc48 as a Moe1-binding protein from a yeast two-hybrid screen, and confirmed biochemically that they form a stable complex in fission yeast. Overexpressing Moe1 or Yin6 partially rescued phenotypes of cdc48 mutants; conversely, overexpressing Cdc48 partially rescued phenotypes of moe1 or yin6 mutants. Mutants defective in both Cdc48 and the Yin6-Moe1 complex showed growth defects that were far more severe than either alone. These double mutants were severely deficient in endoplasmic reticulum associated degradation (ERAD), as they were hypersensitive to accumulation of misfolded proteins. In addition, their chromosomes showed frequent defects in spindle attachment and segregation--these mitotic defects correlated with Ase1 and Bir1/survivin mislocalization. These results suggest that Cdc48, Yin6 and Moe1 act in the same protein complex to concertedly control ERAD and chromosome segregation. Many of these properties are evolutionarily conserved in humans, since human Cdc48 rescued the lethality of the yeast cdc48Delta mutant, and Int6 and Moe1/eIF3d bind Cdc48 in human cells.


Infectious agents associated with respiratory disease in pheasants.
In a case-control study of the infectious agents associated with natural outbreaks of respiratory disease in pheasants, 28 batches of birds from sites affected by disease and eight batches of birds from unaffected sites were examined by six veterinary laboratories in England, Wales and Scotland, and tested for mycoplasmas, other bacteria and viruses. Sinusitis was the commonest sign of disease and was associated with Mycoplasma gallisepticum as detected by PCR in the trachea (P < 0.05) and conjunctiva (P < 0.01). Sinusitis was also associated with pasteurella cultured from the sinus (P < 0.05), antibody to avian pneumovirus (APV) (P < 0.01) and avian coronaviruses as detected by reverse-transcriptase PCR (P < 0.05); there was no association between disease and APV as detected by PCR. Avian coronaviruses were the most common infectious agents detected. They were genetically close to infectious bronchitis virus (IBV) but differed in their gene sequence from all the serotypes of IBV previously identified in domestic fowl, and serological tests with six known IBV types showed little cross reactivity. Mycoplasma species other than M gallisepticum were cultured in 18 batches of pheasants but, with the exception of Mycoplasma gallinaceum, were not associated with disease.


Reducing chances of COVID-19 infection by a cough cloud in a closed space.
The cough of a COVID-19 infected subject contaminates a large volume of surrounding air with coronavirus due to the entrainment of surrounding air in the jet-like flow created by the cough. In the present work, we estimate this volume of the air, which may help us to design ventilation of closed spaces and, consequently, reduce the spread of the disease. Recent experiments [P. P. Simha and P. S. M. Rao, "Universal trends in human cough airflows at large distances," Phys. Fluids 32, 081905 (2020)] have shown that the velocity in a cough-cloud decays exponentially with distance. We analyze the data further to estimate the volume of the cough-cloud in the presence and absence of a face mask. Assuming a self-similar nature of the cough-cloud, we find that the volume entrained in the cloud varies as V = 0.666 c 2 d c 3 , where c is the spread rate and d c is the final distance traveled by the cough-cloud. The volume of the cough-cloud without a mask is about 7 and 23 times larger than in the presence of a surgical mask and an N95 mask, respectively. We also find that the cough-cloud is present for 5 s-8 s, after which the cloud starts dissipating, irrespective of the presence or absence of a mask. Our analysis suggests that the cough-cloud finally attains the room temperature, while remaining slightly more moist than the surrounding. These findings are expected to have implications in understanding the spread of coronavirus, which is reportedly airborne.


Lysosomal alpha-N-acetylgalactosaminidase deficiency, the enzymatic defect in angiokeratoma corporis diffusum with glycopeptiduria.
Recently a novel case of angiokeratoma corporis diffusum with glycoaminoaciduria was described in a 46-yr-old Japanese woman. Known causes of the cutaneous manifestation were eliminated by enzyme analyses, and further characterization of the accumulated urinary O-linked sialopeptides revealed identity to those excreted by patients with an infantile neuroaxonal dystrophy due to lysosomal alpha-N-acetylgalactosaminidase deficiency. Investigation of the alpha-N-acetylgalactosaminidase activity and protein in the proband revealed less than 2% of normal activity and the absence of detectable immunoreactive enzyme protein, findings comparable to those in the patients with infantile neuroaxonal dystrophy and alpha-N-acetylgalactosaminidase deficiency. In addition, the proband's unaffected offspring had half-normal levels of alpha-N-acetylgalactosaminidase activity, consistent with this enzymatic deficiency being the primary metabolic defect in this autosomal recessive trait. Ultrastructural examination of skin and blood cells from the adult proband revealed the presence of prominent lysosomal inclusions containing diffuse amorphous and filamentous material. In contrast, these morphologic findings were not observed in the nonneural tissues from patients with infantile neuroaxonal dystrophy and alpha-N-acetylgalactosaminidase deficiency. These studies document the occurrence of two forms of alpha-N-acetylgalactosaminidase deficiency and sialopeptiduria, a severe infantile-onset form of neuroaxonal dystrophy without angiokeratoma or visceral lysosomal inclusions and an adult-onset form characterized by angiokeratoma, extensive lysosomal accumulation of sialoglycopeptides and the absence of detectable neurologic involvement.


Communicating bronchopulmonary pancreatic foregut malformation.
Bronchopulmonary foregut malformations include intralobar and extralobar pulmonary sequestrations, bronchogenic cysts, and communicating bronchopulmonary foregut malformations (CBPFM). These malformations, formes frustes, originate as developmental abnormalities of ventral foregut budding of the tracheobronchial tree or the gastrointestinal tract. The communication's patency with the parent viscus determines if a contained malformation occurs, or if an abnormal communication persists as a CBPFM. This case demonstrates a unique example of a CBPFM in which the main pancreatic duct communicated with pulmonary parenchyma through a retroperitoneal fistula.


Electrophoretic deposition of TiO2 nanoparticles using organic dyes.
Electrophoretic deposition method has been developed for the deposition of TiO(2) nanoparticles modified with organic dyes. Alizarin red, alizarin yellow and pyrocatechol violet dyes were used for the dispersion and charging of TiO(2) in ethanol and anodic electrophoretic deposition of TiO(2) films. The deposition yield was varied by the variation of dye concentration in suspensions and deposition time. Aurintricarboxylic acid dye was used for the deposition of TiO(2) from aqueous suspensions. It was found that thin films of pure aurintricarboxylic acid and composite aurintricarboxylic acid TiO(2) films can be obtained. The deposition yield was studied by quartz crystal microbalance. Dye film thickness was varied in the range of 0.1-2 μm by variation in the deposition time at a constant voltage. The composition of the films and the amount of the deposited material can be varied by the variation of TiO(2) and dye concentration in suspensions and deposition time. The films were studied by Fourier transform infrared spectroscopy, thermogravimetric analysis, differential thermal analysis and electron microscopy. The deposition mechanisms were discussed. The electrophoretic deposition method offers advantages for the fabrication of dye-sensitized TiO(2) films.


A nomogram to predict recurrence of RA patients in clinical remission within one year.
Some patients with rheumatoid arthritis (RA) will recur despite they have achieved clinical remission after treatment. The subclinical synovitis detected by ultrasonography (US) may be one of the main causes of the RA recurrence. The aim of this study is to establish a nomogram for predicting the outcome of RA patients with disease in clinical remission. One hundred and sixty-seven RA patients who achieved clinical remission and were willing to receive a 1-year follow-up were included in this study. Their demographic, clinical, and laboratory characteristics were recorded at baseline. 7-joints ultrasound (US7) synovitis score (simplified from US7 score) were evaluated at baseline and at the end of follow-up (or when RA recurrence confirmed). All patients were divided into recurrence group and non-recurrence group after the follow-up. Multivariable regression was applied to link the predictors that were significant at p < 0.05 in the univariate analysis and the recurrence of RA patients in clinical remission, which was served as the basis of the nomogram. Fifty-one RA patients were included in the recurrence group and 116 patients in the non-recurrence group. All US7 synovitis scores in this study showed excellent reproducibility. Multivariable analysis revealed that high-titer positive anti-cyclic citrullinated peptide (anti-CCP), simplified clinical disease activity index (SDAI), baseline grayscale ultrasound (GSUS) score, and baseline power Doppler ultrasound (PDUS) score were the independent predictors for RA recurrence within 1 year. A nomogram incorporating the independent predictors was constructed to predict the risk of RA recurrence. The nomogram showed good discrimination (C-index=0.826) and good calibration. The nomogram incorporating anti-CCP, SDAI, and subclinical synovitis helps to achieve complete remission and reduces the risk of short-term recurrence of RA patients.


In vivo three-dimensional spectroscopic photoacoustic imaging for monitoring nanoparticle delivery.
In vivo monitoring of nanoparticle delivery is essential to better understand cellular and molecular interactions of nanoparticles with tissue and to better plan nanoparticle-mediated therapies. We developed a three-dimensional ultrasound and photoacoustic (PA) imaging system and a spectroscopic PA imaging algorithm to identify and quantify the presence of nanoparticles and other tissue constituents. Using the developed system and approach, three-dimensional in vivo imaging of a mouse with tumor was performed before and after intravenous injection of gold nanorods. The developed spectroscopic PA imaging algorithm estimated distribution of nanoparticle as well as oxygen saturation of blood. Moreover, silver staining of excised tumor tissue confirmed nanoparticle deposition, and showed good correlation with spectroscopic PA images. The results of our study suggest that three-dimensional ultrasound-guided spectroscopic PA imaging can monitor nanoparticle delivery in vivo.


Unstable triplet repeat and phenotypic variability of spinocerebellar ataxia type 1.
A Siberian kindred with spinocerebellar ataxia genetically linked to the SCA1 locus on chromosome 6p has been screened for the CAG triplet expansion within the coding region of the SCA1 gene. The kindred includes 1,484 individuals, 225 affected and 656 at risk, making this collection the largest spinocerebellar ataxia type 1 (SCA1) pedigree known. Each of the studied 78 SCA1 patients carried an expanded allele containing a stretch of 39 to 72 uninterrupted CAG repeats. Normal alleles had 25 to 37 trinucleotide repeats. Expanded alleles containing 40 to 55 repeats were found in 26 at-risk relatives. The number of CAG repeats in the mutated allele was inversely correlated with age at disease onset. Cerebellar deficiency was present in each patient and its severity was moderately affected by the number of CAG repeats. In contrast, the associated signs, dysphagia, diffuse skeletal muscle atrophy with fasciculations, and tongue atrophy were absent or mild in patients with low CAG repeat numbers, but severely complicated the course of illness in patients with a larger number of repeat units. One female mutation carrier was asymptomatic at age 66, more than 2 standard deviations beyond the average age of risk, suggesting incomplete penetrance. In 2 symptomatic individuals who had an expanded number of CAG repeats on both chromosomes, age at onset, rate of progression, and clinical manifestation corresponded to the size of the larger allele.


Biochemical and genetic analysis of an antigenic determinant found on N-linked oligosaccharides in Dictyostelium.
Dictyostelium discoideum synthesizes many highly immunogenic carbohydrates of unknown structure and function. We have used monoclonal antibodies prepared against one of these called CA1 to investigate its structure and the consequences of its loss. CA1 is preferentially expressed on lysosomal enzymes as a specific arrangement of mannose-6-SO4 residues on N-linked oligosaccharides. Mutant strains HL241 and HL243 do not express CA1, and synthesize a truncated lipid-linked oligosaccharide (LLO) precursor that lacks the critical mannose residues needed for expression. The lesion appears to result from the loss of mannosyl transferase activity involved in LLO biosynthesis. The truncated LLO is poorly transferred to an artificial peptide acceptor in a cell-free N-glycosylation assay, and this appears to result from improper topological localization of the LLO or to a lower affinity of the LLO for the oligosaccharyl transferase. Although both mutants share these lesions, they are biochemically and genetically distinct. Only HL243 is lower in N-glycosylation in intact cells, and this is not a result of an altered structure of the LLO. There are other differences between the strains. HL241 can form fruiting bodies at a slower rate than normal while HL243 cannot aggregate. Genetic analysis of defects shows that the CA1 lesion in HL241 is recessive, while the lesion in both CA1 and in development are dominant and co-segregate in HL243 and are, therefore, likely to be in the same gene. Lysosomal enzyme targeting is normal but enzyme processing proceeds at a 2-3 fold slower rate in HL241 and HL243 compared to wild-type. Strain HL244 does not express CA1 since it completely lacks protein sulfation, but lysosomal enzyme targeting and processing proceeds at a normal rate, showing that sulfate is not essential for these processes. Alterations in oligosaccharide structure can have individualized effects on the biosynthesis of lysosomal enzymes. The results presented here illustrate how this approach can be used to study both the structure and function of carbohydrate epitopes.


Cyclooxygenase inhibitors suppress angiogenesis and reduce tumor growth in vivo.
Angiogenesis plays a key role in the development of malignant tumors. To clarify the roles of cyclooxygenase (COX) in malignant tumor development and angiogenesis, we investigated the effects of COX inhibitors on two kinds of gastrointestinal cancer xenograft, one of which overexpresses COX-2 and the other expresses no COX, in nude mice in vivo. There was a positive correlation between tumor volume and angiogenesis within the xenograft. Oral administration with a specific COX-2 or a nonspecific COX inhibitors lowered the expression of potent angiogenic factors; vascular endothelial growth factor and basic fibroblast growth factor, reduced angiogenesis and growth, induced apoptosis, and suppressed cell replication of the COX-2 overexpressing cancer xenografts in a dose-dependent manner. A nonspecific COX inhibitor, not a specific COX-2 inhibitor, reduced growth and angiogenesis of non-COX expressing cancer xenograft by inhibition of COX-1 in vascular endothelial cells. These results demonstrate that COX inhibitors suppress angiogenesis and tumor growth by inhibiting expression of angiogenic factors and vascular endothelial cell growth. They support the hypothesis that COX plays an important role in cancer growth via angiogenesis. These findings offer a new strategy against cancer using COX inhibitors (nonsteroidal anti-inflammatory drugs).


Disruption of SEMA4D ameliorates platelet hypersensitivity in dyslipidemia and confers protection against the development of atherosclerosis.
In dyslipidemic states, platelets become hyperreactive, secreting molecules that promote atherosclerosis. We have shown that the semaphorin family member, sema4D (CD100), is expressed on the surface of platelets and proposed that its role includes promoting thrombus growth by binding to nearby platelets and endothelial cells, both of which express sema4D receptors. Here we tested the hypothesis that deleting sema4D will attenuate the adverse consequences of dyslipidemia on platelets and the vessel wall. Platelet function and atherosclerotic lesion formation were measured in LDLR(-/-) and sema4D(-/-)LDLR(-/-) mice after 6 months on a high-fat diet. All of the mice developed the dyslipidemia expected on this diet in the absence of functional LDL receptors. However, when compared to LDLR(-/-) mice, sema4D(-/-) LDLR(-/-) mice had reduced lipid deposition in the descending aorta, a 6-fold decrease in the frequency of arterial occlusion and a reduction to near wild-type levels in the accumulation of platelets after injury. These differences were retained ex vivo, with a marked decrease in platelet accumulation on collagen under flow and in platelet aggregation. These results show that loss of sema4D expression reduces the platelet hyperactivity otherwise found in dyslipidemia, and confers protection against the development of atherosclerosis.


Functional mapping of Saccharomyces cerevisiae Prp45 identifies the SNW domain as essential for viability.
The essential gene product Prp45 (379 aa) of Saccharomyces cerevisiae is a highly conserved, but N-terminally abridged, ortholog of the human transcriptional coactivator SKIP, which is involved in TGFbeta, Notch, and steroid hormone signaling. We used a diploid strain harboring PRP45 deletion, which is inviable in the haploid, to test for complementation with the truncated versions of Prp45. The N-terminal half of the protein (aa 1 to 190), denoted as the SNW domain, was found sufficient to support the essential function. Interestingly, substituting the SNW motif itself with AAA was compatible with viability. GFP-tagged Prp45 was localized in nuclear "speckles" over a diffuse nuclear background. We further found that Prp45 activated the transcription of a reporter gene in S. cerevisiae when targeted to DNA. The observed effect relied in part upon the presence of conserved helical repeats and upon the highly charged C-terminal domain (pI = 11.3). Prp45, which lacks most of the binding motifs of the human ortholog, and whose N-terminal half is sufficient for supporting the growth of prp45 cells, might be helpful in elucidating the essential function of SNW/SKIP proteins.


[Geographic variability of Adh-F allele frequency in populations of Drosophila melanogaster].
Variation of Adh-F allele frequency in seven regions of North and South America, Eurasia, Africa, and Australia was analyzed on the basis of published data. In six regions, regression of Adh-F frequency on latitude was positive; in four regions, slopes of the regression curves were identical. Regression on the average lowest temperature of the coldest month was negative in six regions. No definite trends in regression on the highest temperature of the hottest month and on rainfall in the most humid month and the driest months were found. Geographic differentiation of populations was independent of climatic parameters. Examination of variation in various climatic zones revealed that tropical populations were distinctly different from those from other climatic zones. No climatic differentiation of fixation index FST was detected. These results indicate that Adh polymorphism is maintained by natural selection.


The Influence of Chosen Plant Fillers in PHBV Composites on the Processing Conditions, Mechanical Properties and Quality of Molded Pieces.
This work is inspired by the current European policies that aim to reduce plastic waste. This is especially true of the packaging industry. The biocomposites developed in the work belong to the group of environmentally friendly plastics that can reduce the increasing costs of environmental fees in the future. Three types of short fibers (flax, hemp and wood) with a length of 1 mm each were selected as fillers (30% mass content in PHBV). The biocomposites were extruded and then processed by the injection molding process with the same technical parameters. The samples obtained in this way were tested for mechanical properties and quality of the molded pieces. A significant improvement of some mechanical properties of biocomposites containing hemp and flax fibers and quality of molded pieces was obtained in comparison with pure PHBV. Only in the case of wood-PHBV biocomposites was no significant improvement of properties obtained compared to biocomposites with other fillers used in this research. The use of natural fibers, in particular hemp fibers as a filler in the PHBV matrix, in most cases has a positive effect on improving the mechanical properties and quality of molded pieces. In addition, it should be remembered that the obtained biocomposites are of natural origin and are fully biodegradable, which are interesting and desirable properties that are a part of the current trend regarding the production and commercialization of modern biomaterials.


Mutants in paramecium tetraurelia defective in their axonemal response to calcium.
Six mutants of Paramecium tetraurelia, which display altered axonemal responses to Ca++, are described. The mutants, designated atalantas, are impaired in their ability to swim backward when stimulated by ions or heat; instead they spin very rapidly in one place. Three mutants, ataA1-3, are completely unable to swim backward. The three lines, however, can be distinguished from one another by their forward swimming velocities. The remaining three mutants are leaky. ataB swims backward briefly when stimulated, then stops and spins in place. ataC and ataD are extremely leaky and only display the spinning phenotype at elevated temperatures. An electrophysiological analysis reveals that all six mutants have normal membrane properties, including the Ca++ inward current under voltage clamp. When the membrane is disrupted so as to allow the axoneme free access to Ca++, wild-type cells swim backward, but the mutants do not. These data indicate the site(s) of lesion in the mutants is in the axoneme or in some step linking Ca++ influx and the axoneme, not within the ciliary membrane. These mutants may be useful in investigating the role of Ca++ in the regulation of axonemal motion.


Characterization of motor control in handwriting difficulties in children with or without developmental coordination disorder.
The purpose of this study was to characterize handwriting deficits in children with developmental coordination disorder (DCD) using computerized movement analyses. Seventy-two children (40 females, 32 males; mean age 7 y, SD 7 mo; range 6 y 2 mo to 7 y 11 mo) with handwriting deficits (33 with DCD, 39 without DCD); and 22 age- and sex-matched children without handwriting deficits were asked to perform handwriting tasks on a digital tablet for the collection of kinematic and kinetic data. Practice times required to achieve automation of movement when writing an unfamiliar character were used to assess the motor learning of handwriting. The children were asked to copy three simple and three complex characters, and the velocity and axial pen force used for corresponding strokes were compared. The attainment of automated handwriting was markedly slower in children with handwriting deficits and DCD, who used a faster stroke velocity to write simple characters (1.22 times those without handwriting deficits), but when writing complex characters, their stroke velocity and pen force were lower (0.85 and 0.89 times those without handwriting deficits, respectively). By linking the results with neuromotor control theories, it was determined that children with DCD have difficulties performing the open-loop and closed-loop movements required for fluent handwriting.


MINT: a Molecular INTeraction database.
Protein interaction databases represent unique tools to store, in a computer readable form, the protein interaction information disseminated in the scientific literature. Well organized and easily accessible databases permit the easy retrieval and analysis of large interaction data sets. Here we present MINT, a database (http://cbm.bio.uniroma2.it/mint/index.html) designed to store data on functional interactions between proteins. Beyond cataloguing binary complexes, MINT was conceived to store other types of functional interactions, including enzymatic modifications of one of the partners. Release 1.0 of MINT focuses on experimentally verified protein-protein interactions. Both direct and indirect relationships are considered. Furthermore, MINT aims at being exhaustive in the description of the interaction and, whenever available, information about kinetic and binding constants and about the domains participating in the interaction is included in the entry. MINT consists of entries extracted from the scientific literature by expert curators assisted by 'MINT Assistant', a software that targets abstracts containing interaction information and presents them to the curator in a user-friendly format. The interaction data can be easily extracted and viewed graphically through 'MINT Viewer'. Presently MINT contains 4568 interactions, 782 of which are indirect or genetic interactions.


Pulmonary venous thrombosis in a patient with COVID-19 infection.
Infection with the SARS-COV2 virus (COVID-19) may be complicated by thrombotic diathesis. This complication often involves the pulmonary microcirculation. While macrovascular thrombotic complications of the lung may include pulmonary artery embolism, pulmonary artery thrombus in situ has also been hypothesized. Pulmonary vein thrombosis has not been described in this context. Herein, we provide a case of an otherwise healthy male who developed an ischemic stroke with left internal carotid thrombus. Further imaging revealed pulmonary emboli with propagation through the pulmonary veins into the left atrium. This left atrial thrombus provides a source of atypical "paradoxic arterial embolism". Thrombotic outcomes in the setting of severe COVID 19 pneumonia may include macrovascular venous thromboembolism, microvascular pulmonary vascular thrombosis and arterial thromboembolism. Pulmonary vein, herein described, provides further mechanistic pathway for potential arterial embolic phenomenon.


Adrenergically mediated variations in the energy required to defibrillate the heart: observations in closed-chest, nonanesthetized dogs.
The day-to-day variations in epicardial defibrillation threshold (DFT) were examined in closed-chest, unanesthetized dogs. In 11 animals, DFT decreased from 15.8 +/- 2.1 J (mean +/- SE) at the beginning of the study (day 1), to 7.4 +/- 1.7 J on day 2 (p less than .0001). DFT measured daily for 5 consecutive days in seven dogs decreased from 22.1 +/- 3.1 J on day 1 to 9.3 +/- 2.3 J on day 2 (p less than .01) and remained stable from day 2 to day 5. Transcardiac impedance, measured in six dogs, decreased from 112 +/- 6 omega on day 1 to 100 +/- 6 omega on day 2 (p = NS). Propranolol given on day 2 in 14 dogs increased DFT from 12.0 +/- 2.2 to 18.0 +/- 3.1 J (p less than .05). The effects on DFT of sequential administration of isoproterenol and propranolol were examined in 10 dogs. Isoproterenol decreased DFT from 10.0 +/- 1.9 to 5.5 +/- 1.5 J when given before propranolol (p less than .001, n = 10), and from 11.7 +/- 3.0 to 9.7 +/- 3.1 J when given after propranolol (p less than .05, n = 9). Propranolol increased DFT from 10.6 +/- 3.0 to 14.6 +/- 3.9 J when given before isoproterenol (p less than .02, n = 9), and from 10.7 +/- 1.4 to 14.4 +/- 1.5 J when given after isoproterenol (p less than .01, n = 10). These experiments demonstrate a sustained cardiac effect of epicardial defibrillation reflected by a decrease in DFT that is partially reversible by propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)


Cellular nonmuscle myosins NMHC-IIA and NMHC-IIB and vertebrate heart looping.
Flectin, a protein previously described to be expressed in a left-dominant manner in the embryonic chick heart during looping, is a member of the nonmuscle myosin II (NMHC-II) protein class. During looping, both NMHC-IIA and NMHC-IIB are expressed in the mouse heart on embryonic day 9.5. The patterns of localization of NMHC-IIB, rather than NMHC-IIA in the mouse looping heart and in neural crest cells, are equivalent to what we reported previously for flectin. Expression of full-length human NMHC-IIA and -IIB in 10 T1/2 cells demonstrated that flectin antibody recognizes both isoforms. Electron microscopy revealed that flectin antibody localizes in short cardiomyocyte cell processes extending from the basal layer of the cardiomyocytes into the cardiac jelly. Flectin antibody also recognizes stress fibrils in the cardiac jelly in the mouse and chick heart; while NMHC-IIB antibody does not. Abnormally looping hearts of the Nodal(Delta 600) homozygous mouse embryos show decreased NMHC-IIB expression on both the mRNA and protein levels. These results document the characterization of flectin and extend the importance of NMHC-II and the cytoskeletal actomyosin complex to the mammalian heart and cardiac looping.


Current state of athalassohaline deep-sea hypersaline anoxic basin research-recommendations for future work and relevance to astrobiology.
Deep-sea hypersaline anoxic basins (DHABs) are uniquely stratified polyextreme environments generally found in enclosed seas. These environments select for elusive and widely uncharacterized microbes that may be living below the currently recognized window of life on Earth. Still, there is strong evidence of highly specialized active microbial communities in the Kryos, Discovery, and Hephaestus basins located in the Eastern Mediterranean Sea; the only known athalassohaline DHABs. Life is further constrained in these DHABs as near-saturated concentrations of magnesium chloride significantly reduces water activity (aw ) and exerts extreme chaotropic stress, the tendency of a solution to disorder biomolecules. In this review, we provide an overview of microbial adaptations to polyextremes focusing primarily on chaotropicity, summarize current evidence of microbial life within athalassohaline DHABs and describe the difficulties of life detection approaches and sampling within these environments. We also reveal inconsistent measurements of chaotropic activity in the literature highlighting the need for a new methodology. Finally, we generate recommendations for future investigations and discuss the importance of athalassohaline DHAB research to help inform extraterrestrial life detection missions.


Robotics and coronary artery surgery.
Significant progress in cardiac surgery, and specifically the surgical management of coronary artery disease, has been due in large part to enabling technology. Robotic systems have been recently developed and refined for use in cardiac surgery to facilitate, among other procedures, a totally endoscopic approach to coronary artery bypass surgery. These systems enhance precision through endoscopic approaches by specifically addressing the inherent limitations of conventional endoscopic coronary microsurgical instrumentation via computerized, digital interface, telemanipulation technology. With a combined experience of 125 patients, several groups have independently demonstrated the clinical feasibility of totally endoscopic coronary artery bypass with two commercially available robotic telemanipulation systems. Additional enabling technology is needed to overcome the challenges currently limiting development and widespread application of totally endoscopic off-pump multivessel coronary artery bypass surgery.


[Common variable immunodeficiency (hypogammaglobulinemia of late onset or acquired hypogammaglobulinemia): initial follow-up of 11 cases].
The present paper describes the clinical and laboratory follow-up of 11 patients with the diagnosis of common variable immunodeficiency. Their age varied from 8 to 45 years. The mean disease time was 12.6 years and mean diagnosis time 4.3 years. Infectious manifestations, mainly of the respiratory and digestive tracts, occurred in all patients. Polyadenomegaly was noted in seven, hepatomegaly in six, splenomegaly in five and arthralgia in four patients. All of them presented serum IgG less than 250 mg/dl. IgA less than 33 mg/dl and IgM less than 31 mg/dl, except one with IgM = 176 mg/dl. The isohaemagglutinin titers were less than 1/20 in all but one patient. The determination of the number of B lymphocytes in the peripheral blood revealed normal counts in three, elevated in one and decreased in five patients. The CD-4/CD-8 ratio was less than 1 in 8 and greater than 1 in three of them. Five patients had positive cutaneous late reactions to at least one of the following antigens: PPD, SK-SD (Varidase), Trichophytin and Levedurin (Candidin). A decrease of the proliferative activity of peripheral blood mononuclear cells stimulated by lectins (PHA, Con-A, PWM) was also noted. Natural killer function was decreased. The association a possible role of regulatory lymphocytes in the immunopathogenesis of this disease. The data presented here emphasize the diversity of clinical and immunological manifestations of this disease, which could be noted between diverse patients and in the follow-up of a single one. In our cases the disease had an evolutive character, with a primarily humoral dysfunction followed by cellular immunity disturbances that determined poorer prognosis and progressive difficulties in the therapeutics. We suggest a conceptual reevaluation of this condition and a new denomination, for instance "Late-Onset Combined Immunodeficiency". The long delay between the initial clinical manifestations of the disease and its diagnosis was a handicap for an adequate treatment. Early intervention could certainly decrease the morbidity and mortality of the disease.


Frequency ratio of an 115In+ ion clock and a 87Sr optical lattice clock.
We report on the first, to the best of our knowledge, frequency ratio measurement of an 115In+ singleion clock and a 87Sr optical lattice clock. A hydrogen maser serves as a flywheel oscillator to measure the ratio by independent optical combs. From 89,000 s of measurement time, the frequency ratio fIn/fSr is determined to be 2.952 748 749 874 863 3(23) with 7.7×10-16 relative uncertainty. The measurement creates a new connection in the network of frequency ratios of optical clocks.


Correlations using the NREM-REM sleep cycle frequency support distinct regulation mechanisms for REM and NREM sleep.
Polysomnograms of most homeothermic species distinguish two states, rapid eye movement (REM) and non-REM (NREM) sleep. These alternate several times during the night for reasons and following rules that remain poorly understood. It is unknown whether each state has its own function and regulation or whether they represent two facets of the same process. The present study compared the mean REM/NREM sleep ratio and the mean number of NREM-REM sleep cycles across 3 consecutive nights. The rationale was that, if REM and NREM sleep are tightly associated, their ratio should be comparable whatever the cycle frequency in the night. Twenty-six healthy subjects of both sexes were recorded at their home for 4 consecutive nights. The correlation between the REM/NREM sleep ratio and the number of cycles was highly significant. Of the two sleep components, REM sleep was associated to the number of cycles, whereas NREM sleep was not. This suggests that the relationship between REM sleep and NREM sleep is rather weak within cycles, does not support the concept of NREM-REM sleep cycles as miniature units of the sleep process, and favors the concept of distinct mechanisms of regulation for the two components.


Acemetacin-induced fixed drug eruption.
Fixed drug eruption (FDE) is an adverse effect observed with various drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs) and various antibiotics. Acemetacin, a prodrug of indomethacin, is an NSAID licensed for use in rheumatic disease and other musculoskeletal disorders. We present a case of acemetacin-induced FDE in a 49-year-old woman. To the best of our knowledge, this is the second case report detailing clinical and histopathological findings of a patient with FDE caused by acemetacin.


Peripherin-reactive antibodies in mouse, rabbit, and human blood.
Type 1 diabetes (T1D) is an autoimmune disorder that results from the destruction of insulin-producing beta-cells in the islets of Langerhans. To date, autoimmune T-cell response and antibody reactivity to more than 20 autoantigens have been linked to this disease. Some studies have described the intermediate filament protein peripherin (PRPH) as an autoantigen associated with T1D in non-obese diabetic (NOD) mice. We evaluated immune reactivity of mouse and rabbit sera and human plasma to a 58 kDa protein expressed in RIN-m5F rat insulinoma cells. The protein was isolated using 2-DE and identified by mass spectrometry as PRPH. Antibodies from healthy humans and T1D patients, CD-1 mice, C57BL/6 mice, NOR (non-obese diabetes resistant) mice, and NOD mice reacted with PRPH on Western blots. However, antibody response to PRPH was stronger in NOD than non-autoimmune prone C57BL/6 mice. We conclude that immune reactivity to PRPH is not exclusively associated with NOD mice or human patients with T1D. Furthermore, the frequent occurrence of PRPH-reactive antibodies in mouse and human blood suggests that binding may be non-specific or could reflect the presence of natural autoantibodies against PRPH. These findings point to the need for a re-evaluation of PRPH as a T1D autoantigen in NOD mice and raise the question of the physiological relevance of such widespread immune reactivity against this peripheral nervous system protein.


Mutation in Exon2 of BRCA1 Gene in Adult Bengali Bangladeshi Female Patients with Breast Cancer: An Experience from Two Tertiary-Care Hospitals.
The occurrence rate of BRCA1 mutations is found to be high in South Asian countries where early onset of breast cancer is common. In Bangladesh, noticeable percentage of patients experience breast cancer in their reproductive ages. The objective of this study was to identify any mutation in exon2 of the BRCA1 gene in adult Bengali Bangladeshi female patients with breast cancer. In this cross-sectional descriptive study, the genomic DNA was extracted from the blood of adult fifty Bengali Bangladeshi female breast cancer patients. The whole region of exon2 of the BRCA1 gene was amplified and the amplified DNA products were sequenced using Sanger sequencing. The raw chromatogram data were analyzed using Chromas software, and analyzed sequences were compared with the NCBI RefSeq database by BLAST search. The resultant amino acid change was detected by MEGA X software. We found the mean age at diagnosis 44.66 years, whereas 96% of patients were married, 90% were multiparous and 86% breastfed their children. All patients had unilateral breast cancer and among them 94% had invasive ductal carcinoma. Only 24.5% of the patients had associated omorbidity. The family history of breast cancer or other BRCA-associated cancer was positive only for 4% of patients. A total of five mutations were identified all of which caused by substitutions. Among them three were nonsynonymous and two were synonymous. Only 2.5% of the patients, within the age group of 18-50 years, were found to have mutations in their blood, whereas 26.66% of the patients above 50 years found to have mutations in this study. Among this small sample size, we found five mutations in exon2 of the BRCA1 gene and this indicates the necessity to find out the mutation spectra of the BRCA1 gene in the Bangladeshi population.


Mammosomatotropes are abundant in bovine pituitaries: influence of gonadal status.
Mammosomatotropes--cells that secrete both GH and PRL--are a common pituitary cell type in a variety of mammalian species. Recently, immunogold electron microscopy was used to demonstrate that all acidophils (a generic term used here to denote cells which secrete GH and/or PRL) in cattle stain for both GH and PRL. This high degree of overlap, which is unique among the mammalian species examined in this regard, raises the question: do all acidophils actively release both hormones concurrently? In the present study, we addressed this question by employing reverse hemolytic plaque assays to measure GH and PRL release from individual bovine pituitary cells in culture in the presence of stimulatory secretagogues. Inconsistent with the previous reports on hormone storage, all bovine acidophils in gonad-intact and castrated males did not actively release both GH and PRL. In gonad-intact males approximately 9% of all pituitary cells released both hormones, whereas 21% released only GH and 45% PRL alone. In castrated males, mammosomatotropes comprised only 22% of the pituitary cell population, whereas GH-only cells accounted for 8% and PRL secretors 46%. This divergence in the relative proportions of GH-only cells and mammosomatotropes suggests that the hormonal milieu plays an important role in maintenance of the various acidophilic cell types. In addition, the reciprocal relationship between cells that released GH-only and dual hormone secretors in the two models studied supports the possibility that these cell types are functionally interconvertible.


Analysis on the erythrocyte shape changes using wavelet transforms.
The mechanics of red blood cell shape changes under normal and deformed conditions are analyzed using wavelet based approach. Images of intact and deformed human red blood cells obtained from normal adults are subject to morphological image processing and the corresponding shape descriptions at two different levels of approximations using different wavelet functions are analyzed. The results demonstrate that using wavelets it is possible to classify normal and deformed red blood cell shapes. Uniform and consistent results are obtained for cells with similar shapes, for all chosen wavelet functions. The variation indices are significant (p < 0.005) for all the chosen wavelet functions at both the approximation levels. Further it seems that this approach could be useful for identifying closely identical cell shapes. As cell shape deformations are significant in describing the flow behavior in micro or macro vessels the study seems to be clinically relevant. The methodologies, algorithms and observations based on wavelet based analysis are discussed in detail.


Robust association of the LPA locus with low-density lipoprotein cholesterol lowering response to statin treatment in a meta-analysis of 30 467 individuals from both randomized control trials and observational studies and association with coronary artery disease outcome during statin treatment.
The LPA single-nucleotide polymorphism rs10455872 has been associated with low-density lipoprotein cholesterol (LDLc) lowering response to statins in several randomized control trials (RCTs) and is a known coronary artery disease (CAD) marker. However, it is unclear what residual risk of CAD this marker may have during statin treatment. Using electronic medical records linked to the GoDARTS genotyped population, we identified over 8000 patients on statins in Tayside, Scotland. We replicated the findings of the RCTs, with the G allele of rs10455872 being associated with a 0.10 mmol/l per allele poorer reduction in LDLc in response to statin treatment, and conducted a meta-analysis with previously published RCTs (P = 1.46 × 10, n = 30 467). We showed an association between rs10455872 and CAD in statin-treated individuals and have replicated this finding in the Utrecht Cardiovascular Pharmacogenetics study (combined odds ratio 1.41, 95% confidence interval 1.17-1.68, P = 4.5 × 10, n = 8822) suggesting that statin treatment does not abrogate this well-established genetic risk for CAD. Furthermore, in a Cox proportional hazards model with LDLc measured time dependently, we demonstrated that the relationship between CAD and rs10455872 was independent of LDLc during statin treatment. Individuals with the G allele of rs10455872, which represents approximately one in seven patients, have a higher risk of CAD than the majority of the population even after treatment with statins; and therefore represent a vulnerable group requiring an alternative medication in addition to statin treatment.


Attenuation of green fluorescent protein half-life in mammalian cells.
The half-life of the green fluorescent protein (GFP) was determined biochemically in cultured mouse LA-9 cells. The wild-type protein was found to be stable with a half-life of approximately 26 h, but could be destabilized by the addition of putative proteolytic signal sequences derived from proteins with shorter half-lives. A C-terminal fusion of a PEST sequence from the mouse ornithine decarboxylase gene reduced the half-life to 9.8 h, resulting in a GFP variant suitable for the study of dynamic cellular processes. In an N-terminal fusion containing the mouse cyclin B1 destruction box, it was reduced to 5.8 h, with most degradation taking place at metaphase. The combination of both sequences produced a similar GFP half-life of 5.5 h. Thus, the stability of this marker protein can be controlled in predetermined ways by addition of the appropriate proteolytic signals.


Decoherence of orbital angular momentum tangled photons in non-Kolmogorov turbulence.
Orbital angular momentum (OAM) entangled photons propagating through non-Kolmogorov turbulence are studied by numerical simulations. Here, the paper uses the multiphase screen model, especially focusing on the influences of the azimuthal mode and the turbulence parameters (i.e., the generalized exponent, the outer scale of turbulence, and the inner scale of turbulence) on entanglement evolution in the weak scintillation regime. The results indicate that the azimuthal mode, the generalized exponent, and the outer scale of turbulence have obvious influences on OAM entanglement. However, the influence of the turbulence inner scale on OAM entanglement can be ignored.


Oral Health Behaviors among Schoolchildren in Western Iran: Determinants and Inequality.
Little information exists on the status of oral hygiene behavior (OHB) and socioeconomic inequalities in developing countries like Iran. The aim of this study was to assess OHB and its determinants and socioeconomic inequality among schoolchildren in western Iran during 2018. A cross-sectional survey was conducted on 1,457 students aged 12-15 years living in Kermanshah city, western Iran. We used multistage sampling to select the samples. A self-administrated questionnaire was used to collect data on OHB, sociodemographic characteristics, and economic status of the households of students. Multivariate logistic regression was used to examine the association between OHB and its determinants. We used the relative concentration index, normalized (RCIn) and a concentration curve (CC) to examine socioeconomic-related inequality in OHB. The study indicated that crude and age-adjusted prevalence of good OHB was 14.61% (95% CI 12.89%-16.53%) and 15.17% (95% CI 13.22%-17.35%), respectively. Logistic regression analysis showed that sex, mother's education, socioeconomic status, and oral health literacy had a statistically significant positive impact on OHB. RCIn (0.2582, 95% CI0.1770-0.3395) values and the CC indicated that good OHB was more concentrated among the richer children. This study provides evidence that good OHB was less prevalent, signifying that oral health remains a public-health concern in Iran. Effective polices aimed at improving the socioeconomic status of households and mother's education can contribute positively and to the prevention of oral disorders among schoolchildren.


LARP1 predict the prognosis for early-stage and AFP-normal hepatocellular carcinoma.
The La-related protein 1 (LARP1) has been found to be a RNA binding protein and was related to spermatogenesis, embryogenesis and cell-cycle progression. The aim of this study was to investigate the prognostic value of LARP1 in hepatocellular carcinoma (HCC). LARP1 expression was examined in 15 HCC cell lines and 272 clinical specimens using real-time PCR, immunohistochemistry (IHC) and western blot analysis (WB). LARP1 expression was also studied in 6 paired HCC lesions and the adjacent non-cancerous tissue samples. Statistical analyses were applied to derive association between LARP1 expression scores and clinical characters as well as patient survival. mRNA and protein levels of LARP1 were higher in HCC cell lines and HCC lesions than in normal liver epithelial cells and the paired adjacent noncancerous tissues. LARP1 expression was correlated to survival time, vital status, tumor size and Child-Pugh score. Overall survival analysis showed HCC patients with high LARP1 expression level had lower survival rate (P<0.01). Importantly, this correlation remained significant in patients with early-stage HCC or with normal serum AFP level. LARP1 protein may represent a promising biomarker for predicting the prognosis of HCC, including in early-stage and AFP-normal patients.


3D Bioprinted Patient-Specific Extracellular Matrix Scaffolds for Soft Tissue Defects.
Soft tissue injuries such as volumetric muscle loss (VML) are often too large to heal normally on their own, resulting in scar formation and functional deficits. Decellularized extracellular matrix (dECM) scaffolds placed into these wounds have shown the ability to modulate the immune response and drive constructive healing. This provides a potential solution for functional tissue regeneration, however, these acellular dECM scaffolds are challenging to fabricate into complex geometries. 3D bioprinting is uniquely positioned to address this, being able to create patient-specific scaffolds based on clinical 3D imaging data. Here, a process to use freeform reversible embedding of suspended hydrogels (FRESH) 3D bioprinting and computed tomography (CT) imaging to build large volume, patient-specific dECM patches (≈12 × 8 × 2 cm) for implantation into canine VML wound models is developed. Quantitative analysis shows that these dECM patches are dimensionally accurate and conformally adapt to the surface of complex wounds. Finally, this approach is extended to a human VML injury to demonstrate the fabrication of clinically relevant dECM scaffolds with precise control over fiber alignment and micro-architecture. Together these advancements represent a step towards an improved, clinically translatable, patient-specific treatment for soft tissue defects from trauma, tumor resection, and other surgical procedures.


Detecting falls by analyzing angular momentum.
The aim of the present pilot study is to investigate the hypothesis that fall detection systems based on sensors placed on the distal segments of the body are more effective than solution based on placing sensors on the trunk. To test this hypothesis, we observed the contribution of all body segments to the 3D angular momentum. Five healthy adults were enrolled for the experimental sessions. A set of 39 spherical markers was located on body landmarks and subjects underwent perturbed walking while a Motion Analysis System recorded 3D kinematics. From a biomechanical model, the angular momentum pattern related to each body segment was estimated. Data were post-processed with a threshold-based algorithm used to detect which among body segments allows detect as soon as possible and with limited false alarms the perturbation. Results showed that hands-forearms and chest-head are the most sensitive to external moments orientated along respectively the anterior-posterior and medio-lateral directions.


Maximal Velocity as a Discriminating Factor in the Performance of Loaded Squat Jumps.
To determine what variables determine the differences in performance on 2 tests of squat jump (SJ) performed under light load in highly trained athletes using maximal velocity (Vmax) or flight time (FT) as the discriminating factor of SJ performance. Thirty-two participants performed 2 maximal weighted SJs using a force platform synchronized with a linear transducer. Mean force (Fmean), mean and maximal power (Pmean, Pmax), peak force (PF), maximal rate of force development (RFDmax), and time required to attain PF (TPF) and RFDmax (TRFDmax) were analyzed. SJs were divided into 2 segments: from the initiation of force application to PF1 and from the moment after PF1 to Vmax. Traditional significance statistics revealed significant differences in the same variables between best and worst SJs using both FT and Vmax. However, to use an approach based on the magnitude of the effect, the best SJ showed greater Pmax (83/17/0%), Pmean (85/15/0%), Fmean (71/29/0%), RFDmax1 (73/27/0%), and PF1 (53/47/0%) and lower TPF2 (0/61/39%) than the worst SJ when Vmax was used to discriminate SJ performance. However, using FT to differentiate SJ performance, no difference was observed between best and worst. Although jump height assessed through FT is a valid measure, these results suggest that Vmax is a more sensitive variable than FT to detect differences in loaded-SJ performance.


Prevention of Action of Far-Red-Absorbing Phytochrome in Rumex crispus L. Seeds by Ethanol.
Phytochrome-enhanced germination of curled dock (Rumex crispus L.) seeds is further stimulated by pretreatments in solutions of 0.5 to 2 molar methanol and 0.03 to >/= 0.3 molar 2-propanol during a 2-day 20 degrees C imbibition. Similar pretreatments in 0.1 molar ethanol, acetaldehyde, and n-propanol inhibit phytochrome-enhanced germination. If exposure to ethanol is delayed until 16 hours after a red irradiation, seeds escape the ethanol inhibition indicating a mechanism other than toxicity. The rate of escape from ethanol inhibition roughly parallels the escape from phytochrome control in seeds held in water only, indicating possible ethanol effects on phytochrome. It was found that ethanol pretreatment prevents the far-red absorbing form of phytochrome (Pfr) from acting but does not accelerate dark decay or prevent transformation. Ethanol inhibition may be prevented if ethanol pretreatment is at 10 degrees C instead of 20 degrees C, or may be overcome by transferring ethanol-pretreated seeds to 10 degrees C in water. Similarly, ethanol inhibition can be overcome by a 2-hour 40 degrees C temperature shift concluding the pretreatment. It is proposed that the ethanol causes perturbations at a membrane which prevent Pfr from acting.


Oral Vaccine Delivery for Intestinal Immunity-Biological Basis, Barriers, Delivery System, and M Cell Targeting.
Most currently available commercial vaccines are delivered by systemic injection. However, needle-free oral vaccine delivery is currently of great interest for several reasons, including the ability to elicit mucosal immune responses, ease of administration, and the relatively improved safety. This review summarizes the biological basis, various physiological and immunological barriers, current delivery systems with delivery criteria, and suggestions for strategies to enhance the delivery of oral vaccines. In oral vaccine delivery, basic requirements are the protection of antigens from the GI environment, targeting of M cells and activation of the innate immune response. Approaches to address these requirements aim to provide new vaccines and delivery systems that mimic the pathogen's properties, which are capable of eliciting a protective mucosal immune response and a systemic immune response and that make an impact on current oral vaccine development.