The use of BoneSource hydroxyapatite cement for traumatic metaphyseal bone void filling.
This prospective, randomized study was performed to determine whether a new, in situ setting hydroxyapatite cement is as safe or effective as autologous cancellous bone graft for the treatment of metaphyseal bone voids secondary to trauma. This was a multicenter study including Level I trauma centers and university hospitals. Thirty-eight patients who sustained an acute closed or open type I fracture of the humerus, radius, ulna, femur, tibia, or calcaneus and had a traumatic bone void requiring grafting of the metaphyseal or cancellous bone area were enrolled. Open reduction and internal fixation of the fracture was performed with use of either autologous cancellous bone or BoneSource hydroxyapatite cement to fill traumatic metaphyseal voids. Main outcome measures included maintenance of reduction, fracture healing, pain at defect site, pain at donor site, and clinical function of the limb. Patients treated with BoneSource had an 83% success rate in maintaining reduction, whereas patients treated with autograft had a 67% success rate. A successful clinical outcome, as measured by a healed fracture with minimal to no pain, moderate to maximum function, and no or minor donor site complications, was seen in 69% of patients treated with BoneSource and 57% of patients treated with autograft. In patients with at least 1 year of follow-up, the overall success rate was 79% in the BoneSource group and 70% in the autograft group. BoneSource is safe and effective when used to fill traumatic metaphyseal bone voids. It is at least as good as autograft for treatment of these defects.


[Analysis of drug resistance and risk factors of Enterobacteriaceae in burn units].
To study the risk factors of infection of extended-spectrum beta-lactamases (ESBL)-producing strains and drug resistance of Enterobacteriaceae that infected burn patients. A retrospective study was performed on clinical information of 92 patients with Enterobacteriaceae infection in our burn unit from January 2001 to December 2008. The distribution and drug resistance of Enterobacteriaceae, and the detection rate, drug resistance of ESBL-producing strains, and its risk factors of nosocomial infection were analyzed. Data were processed with Chi-square test. One hundred and nine strains of Enterobacteriaceae were isolated, with 38 (34.9%) strains of Enterobacter cloacae, 25 (22.9%) strains of Escherichia coli, 22 (20.2%) strains of Klebsiella pneumoniae, 13 (11.9%) strains of Proteus mirabilis, and 11 (10.1%) other strains of Enterobacteriaceae. Enterobacteriaceae were moderately or highly resistant to antibiotics except imipenem, resistance rate of which was less than 8.0%. ESBL-producing strains accounted for 44.0% in Escherichia coli, and 77.3% in Klebsiella pneumoniae. Drug-resistance rate of ESBL-producing strains to antibiotics was obviously higher than that of non ESBL-producing strains. Length of hospital stay longer than 20 days, and use of the third-generation cephalosporin longer than 5 days, quinolone antibiotics longer than 7 days, and topical antibiotics longer than 5 days were the risk factors of nosocomial infection caused by ESBL-producing strains, comparing with non ESBL-producing strains, the difference was statistically significant (with chi2 value respectively 5.491, 4.441, 15.186, 4.938, P values all below 0.05). Enterobacteriaceae strains in burn unit of our hospital are highly drug resistant, with high lactamase-producing rates, calling for intense monitor to control the risk factors that predispose the infection of ESBL-producing strains in order to lower the infection rate.


In vitro transcription of Drosophila rRNA genes shows stimulation by a phorbol ester and serum.
The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) and serum both stimulate rapid increases in the transcription of Drosophila rRNA genes in vivo. Here we report that this stimulation is observed in in vitro transcription assays using nuclear extracts from cells treated with TPA or serum. Experiments in which extracts from TPA- or serum-treated cells were mixed with extracts from cells grown in serum-restricted medium showed that there was an increased RNA polymerase I (Pol I) activity present in the cell extracts from treated cells. We used a series of plasmids that had been deleted in the region 5' to the start site of rRNA transcription to determine which sequences were necessary to support the increased transcription seen in extracts from stimulated cells. DNA templates that contain sequences between -150 and +32 (with +1 as the Pol I transcription start site) show dramatic increases in transcription with TPA- and serum-stimulated cell extracts; however, templates that contain 5' sequences to -60 or -43 show at most one-third of the stimulation level of transcription in nuclear extracts from treated cells in comparison with untreated cell extracts. The 5' deletion to -34 abolishes the stimulation effect and drops the basal-level transcription by 20-fold. These results indicate that the regulation of Pol I transcription in Drosophila cells by serum and TPA requires two DNA elements, sequences from -150 to -60 (upstream control element) and sequences from -43 to -34 (a portion of the core promoter.


Endoscopic removal of a right main bronchus glomus tumor.
Glomus tumours in the respiratory tract are very rare. The majority of the reported cases have been surgically treated. An approach with rigid bronchoscopy to endobronchial lesions suspected to be carcinoid or other well vascularized tumours, as glomus tumor is, should be considered because it can allow a safe diagnosis and eventually be therapeutic avoiding more invasive and surgical procedures.


Effects of supplementing growing steers with high levels of partially hydrogenated tallow on feed intake, digestibility, live weight gain, and carcass characteristics.
Effects of supplementing growing steers consuming forage-based diets with high levels of partially hydrogenated tallow on feed intake, digestibility, live weight gain, and carcass characteristics were determined in this study. In Exp. 1, Holstein steer calves were fed bermudagrass hay alone (Control) and with a ground corn-based concentrate at .95% BW (DM basis) plus partially hydrogenated tallow at 0 (Basal), .33 (low fat; LF), or .67% BW (high fat; HF) in a Latin square. Total DMI was increased by concentrate supplementation and was lower for HF than for LF (P < .05; 3.18, 3.83, 4.25, and 3.17 kg/d for Control, Basal, LF, and HF, respectively). In Exp. 2, grazing Angus x Hereford steers (270 kg +/- .4 initial shrunk BW) were fed the same supplements as in Exp. 1 for 84 or 98 d and slaughtered. Live weight gain was increased (P < .05) by concentrate supplementation (1.01, 1.34, 1.41, and 1.30 kg/d for Control, Basal, Low, and High, respectively). The concentration of total lipids in longissimus muscle was 2.51, 2.53, 3.05, and 3.03% of wet tissue for Control, Basal, LF, and HF, respectively (Basal > the mean of LF and HF; P < .07); the proportion of palmitic acid in total fatty acids was similar among treatments. Fat supplementation did not markedly affect sensory, taste, or tenderness characteristics of longissimus muscle. In conclusion, supplementing grazing beef steers with high levels of partially hydrogenated tallow, with slaughter at approximately 400-kg shrunk BW, tended to increase fat in longissimus muscle without altering the palmitic acid level in fatty acids, although sensory, taste, and tenderness characteristics were not modified.


The genetic architecture of low-temperature adaptation in the wine yeast Saccharomyces cerevisiae.
Low-temperature growth and fermentation of wine yeast can enhance wine aroma and make them highly desirable traits for the industry. Elucidating response to cold in Saccharomyces cerevisiae is, therefore, of paramount importance to select or genetically improve new wine strains. As most enological traits of industrial importance in yeasts, adaptation to low temperature is a polygenic trait regulated by many interacting loci. In order to unravel the genetic determinants of low-temperature fermentation, we mapped quantitative trait loci (QTLs) by bulk segregant analyses in the F13 offspring of two Saccharomyces cerevisiae industrial strains with divergent performance at low temperature. We detected four genomic regions involved in the adaptation at low temperature, three of them located in the subtelomeric regions (chromosomes XIII, XV and XVI) and one in the chromosome XIV. The QTL analysis revealed that subtelomeric regions play a key role in defining individual variation, which emphasizes the importance of these regions' adaptive nature. The reciprocal hemizygosity analysis (RHA), run to validate the genes involved in low-temperature fermentation, showed that genetic variation in mitochondrial proteins, maintenance of correct asymmetry and distribution of phospholipid in the plasma membrane are key determinants of low-temperature adaptation.


Antibodies to synthetic platelet-activating factor (1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine) analogues with substituents at the sn-2 position.
We obtained rabbit antibodies by injecting immunogenic conjugates which were prepared by combining covalently 1-O-(15'-carboxypentadecyl)-2-O-acetyl-sn-glycero-3- phosphocholine(acetyl-CPGPC), 1-O-(15'-carboxypentadecyl)-2-O-N,N-dimethylcarbamoyl-sn-glycero-3 - phosphocholine (dimethylcarbamoyl-CPGPC), or 1-O-(15'-carboxypentadecyl)-2-O-N-butyl-carbamoyl-sn-glycero-3-pho sphocholine (butylcarbamoyl-CPGPC) with protein (BSA or KLH), respectively, and examined the specificity of the resulting antibodies by comparison with inhibition of the binding of iodolabeled CPGPC derivatives to the antibodies by corresponding or related phospholipids. Acetyl-CPGPC and dimethylcarbamoyl-CPGPC possessed haptenic activity causing production of antibodies reactive with PAF. Changes of the substituents at sn-2 in the antigens affected the specificity of the resulting antibodies. The affinity of the substituents to the antibodies decreased in the following order: acetyl much greater than dimethylcarbamoyl and butylcarbamoyl for antibodies to acetyl-CPGPC-KLH; dimethylcarbamoyl greater than acetyl much greater than butylcarbamoyl for antibodies to dimethylcarbamoyl-CPGPC-BSA; and butylcarbamoyl greater than dimethylcarbamoyl greater than acetyl for antibodies to butylcarbamoyl-CPGPC-BSA. Naturally occurring phospholipids, including lysoPAF, phosphatidylcholine, lysophosphatidylcholine, and sphingomyelin, revealed no cross-reactivities with these antibodies. Anti-dimethylcarbamoyl-CPGPC-BSA IgG and anti-acetyl-CPGPC-KLH IgG inhibited a PAF-induced aggregation of washed rabbit platelets in a dose-dependent manner. In contrast, anti-butylcarbamoyl-CPGPC-BSA IgG did not affect a PAF-induced platelet aggregation, nor did preimmune IgG.


Attachment of kinetochores to spindle microtubules during meiosis I of Lilium microsporocytes.
Kinetochores and microtubules were visualized simultaneously during spindle formation at the first meiotic division in microsporocytes of Lilium longiflorum (2n = 24) under a confocal laser-scanning microscope, after immunofluorescence staining with centromere-recognizing antiserum and tubulin-specific antibody. During early prometaphase I, each kinetochore of bivalent chromosomes appeared to be an amorphous flat structure upon its initial attachment to microtubules. It became compact and spherical with the development of the spindle. From late prometaphase I, when the bipolar spindle was nearly complete, each kinetochore resembled a double disk that was suggestive of a pair of sister kinetochores and the homologous kinetochores were oriented towards opposite poles. Thus, the bipolar spindle at metaphase I included 12 bivalent chromosomes with a total of four kinetochores each. At anaphase I, the sister kinetochores moved to the same spindle pole as a paired unit. In microsporocytes arrested at prometaphase I by colchicine treatment, the sister kinetochores also came to be distinguishable. These results suggest that the change of kinetochore structure during meiosis I may be under chromosomal control but be somewhat associated with its attachment to spindle microtubules.


Design of a multifunctional nanohybrid system of the phytohormone gibberellic acid using an inorganic layered double-hydroxide material.
To offer a multifunctional and applicable system of the high-value biotechnological phytohormone gibberellic acid (GA), a nanohybrid system of GA using the inorganic Mg-Al layered double-hydroxide material (LDH) was formulated. The ion-exchange technique of LDH was applied to synthesize the GA-LDH hybrid. The hybrid structure of GA-LDH was confirmed by different spectroscopic techniques. The nanohybrid size was described by SEM to be ∼0.1 μm. The GA-LDH nanohybrid structure was the key parameter that controlled GA properties. The layered molecular structure of LDH limited the interaction of GA molecules in two-dimensional directions. Accordingly, GA molecules did not crystallize and were released in an amorphous form suitable for dissolution. At various simulated soil solutions, the nanohybrids showed a sustained release process following Higuchi kinetics. The biodegradation process of the intercalated GA showed an extended period of soil preservation as well as a slow rate of degradation.


Prevalence of obesity and affecting factors in physically disabled adults living in the city centre of Malatya.
The purpose of this study was to investigate the prevalence of obesity, and the risk factors associated with it, in physically disabled adults living in the city centre of Malatya, Turkey. This research was designed as a cross-sectional study conducted on physically disabled people aged 20-65 years living in the city centre of Malatya. The prevalence of obesity in disabled people was within 95% CIs, the power was calculated as 80%, and the sample size of our population was calculated as 258 individuals. The prevalence of obesity was found to be 13.2%. The relationship between disability type and obesity status was found to be significant. The prevalence of obesity was 21.3% in visually impaired people, 17.9% in speech-impaired people, 17.8% in hearing-impaired people and 6.5% in orthopaedically disabled people. Educational interventions on nutrition and lifestyle can be effective considering the high prevalence of obesity in visually impaired people, the prevalence of weakness in orthopaedically disabled people and the risk related to the area in which body fat is localised even when body mass index is within the normal range. Training disabled people in sports appropriate to their disability type and building appropriate facilities for those sports might have a positive effect.


Crosstalk between autophagy and apoptosis in heart disease.
Autophagy is a cell survival mechanism that involves degradation and recycling of cytoplasmic components, such as long-lived proteins and organelles. In addition, autophagy mediates cell death under specific circumstances. Apoptosis, a form of programmed cell death, has been well characterized, and the molecular events involved in apoptotic death are well understood. Damaged cardiomyocytes that show characteristics of autophagy have been observed during heart failure. However, it remains unclear whether autophagy is a sign of failed cardiomyocyte repair or is a suicide pathway for the failing cardiomyocytes. Although autophagy and apoptosis are markedly different processes, several pathways regulate both autophagic and apoptotic machinery and autophagy can cooperate with apoptosis. This review summarizes the evidence for crosstalk between autophagy and apoptosis.


Pharmacologic manipulation of random skin flaps with pentoxifylline.
The literature demonstrates inconsistent results amongst investigators who have used pentoxifylline in an effort to enhance skin flap survival. This study employed a standardized skin flap model in the rat and a standard intraperitoneal dose of pentoxifylline (10 mg/kg) delivered in four different temporal regimens. Fluorescein staining and length of flap survival were measured. The only regimen that demonstrated increased flap survival over saline controls included administration of the drug immediately upon raising the flap and every 12 hours for the next 7 days. Three different regimens that included preoperative administration of the drug failed to demonstrate a beneficial effect on skin flap survival. Slight improvement in flap survival was seen in animals receiving fluorescein. These results suggest an inconsistent pentoxifylline effect even within a single controlled study.


Positive allosteric modulators (PAMs) of metabotropic glutamate receptor 5 (mGluR5) attenuate microglial activation.
Traumatic brain injury causes progressive neurodegeneration associated with chronic microglial activation. Recent studies show that neurodegeneration and neuroinflammation after traumatic brain injury can be inhibited as late as one month in animals by the activation of the metabotropic glutamate receptor 5 in microglia using (RS)-2-chloro-5- hydroxy-phenylglycine. However, the therapeutic potential of this agonist is limited due to its relatively weak potency and brain permeability. To address such concerns, we evaluated the anti-inflammatory activities of several positive allosteric modulators using various in vitro assays, and found that 3,3'-difluorobenzaldazine, 3-cyano-N-(1,3-diphenyl-1H-pyrazol- 5-yl)benzamide and 4-nitro-N-(1-(2-fluorophenyl)-3-phenyl-1H-pyrazol-5-yl)benzamide showed significantly improved potency which makes them potential lead compounds for further development of positive allosteric modulators for the treatment of traumatic brain injury.


Mathematical and statistical models for the control of mosquito-borne diseases: the experience of Costa Rica.
To summarize the results of research conducted in Costa Rica in which mathematical and statistical methods were implemented to study the transmission dynamics of mosquito-borne diseases. Three articles with mathematical and statistical analysis on vector-borne diseases in Costa Rica were selected and reviewed. These papers show the value and relevance of using different quantitative methods to understand disease dynamics and support decision-making. The results of these investigations: 1) show the impact on dengue case reports when a second pathogen emerges, such as chikungunya; 2) recover key parameters in Zika dynamics using Bayesian inference; and 3) show the use of machine learning algorithms and climatic variables to forecast the dengue relative risk in five different locations. Mathematical and statistical modeling enables the description of mosquito-borne disease transmission dynamics, providing quantitative information to support prevention/control methods and resource allocation planning.


Regenerative Endodontic Treatment versus Apical Plug in Immature Teeth: Three-Year Follow-Up.
This report compares and evaluates the treatment outcomes of regenerative endodontic treatment and apical plug as two accepted treatment protocols in a pair of necrotic immature maxillary central incisors of a 12-year old female. The patient was referred complaining of a dull pain and swelling in her upper lip area. She had a history of trauma to the anterior maxilla two years earlier. Both teeth were clinically diagnosed with pulp necrosis and periapical radiographs revealed that separate periapical radiolucent lesions surrounded the immature apices of both teeth. The left and right incisors were treated with apical plug and regenerative endodontic treatment, respectively, using calcium-enriched mixture (CEM) cement. The patient was followed-up for three years. During this period, both teeth were clinically asymptomatic and showed complete radiographic healing of the periapical lesions. The right central incisor showed root development. No tooth discoloration was evident. Apexification by apical plug placement and pulp regeneration are both reliable treatments for immature non-vital teeth. In order to choose the right treatment the advantages of either technique should be weighed against its drawbacks. CEM cement can be successfully applied for both purposes. This biomaterial causes less discoloration of the tooth.


Long-lived frequency shifts observed in a magnetic resonance force microscope experiment following microwave irradiation of a nitroxide spin probe.
We introduce a spin-modulation protocol for force-gradient detection of magnetic resonance that enables the real-time readout of longitudinal magnetization in an electron spin resonance experiment involving fast-relaxing spins. We applied this method to observe a prompt change in longitudinal magnetization following the microwave irradiation of a nitroxide-doped perdeuterated polystyrene film having an electron spin-lattice relaxation time of [Formula: see text]. The protocol allowed us to discover a large, long-lived cantilever frequency shift. Based on its magnitude, lifetime, and field dependence, we tentatively attribute this persistent signal to deuteron spin magnetization created via transfer of polarization from nitroxide spins.


[A method for studying the morbidity risk for sexually transmitted infections in youthful populations].
The method, developed on the basis of disperse analysis, includes anonymous questioning by multicomponent questionnaires containing several blocks of questions which cover the social composition, level of knowledge, behavioral and sexual orientation, control of the reliability of answers, etc. The correlative dependence of individual blocks permits the evaluation of the level and dynamics of the formation of microsocial environment at an institution. The use of this method makes it possible to differentiate youth subpopulations by the epidemiological importance of their risk of infection and its elements in the structure of an individual institution, to find out behavioral "groups of risk" and, in accordance with the data thus obtained, to build the system of propaganda adapted to these individual subpopulations and to the whole institution.


Antimalarial and Antileishmanial Activities of Phytophenolics and Their Synthetic Analogues.
Thirty-seven phytophenolics and their synthetic analogues were evaluated for activity against two protozoal pathogens, Leishmania donovani and Plasmodium falciparum (D6 and W2 clones), respectively. 4,6-Dimethoxyaurone demonstrated the highest activity with IC50 values of 13.2 and 16.9 μm against L. donovani and P. falciparum (W2 clone), respectively, without undesired cytotoxicity against VERO cells. The moiety having two benzene rings was critical to maintain the antiprotozoal activities based on the observation that both coumaranones and chromones were inactive while other test compounds, including coumarans and aurones, remained active. There was no correlation between antiprotozoal activities and previously evaluated insect antifeedant activity against common cutworms (Spodoptera litura). Flavonoids, including aurones, pterocarpans, and lignan like dihydrobenzofurans, structural analogues of coumarans, are abundant in fruits and vegetables, so these phytophenolics may act as natural antiprotozoal agents in humans.


A new plasma-adapted hydroxyethyl starch preparation: in vitro coagulation studies.
Preparing hydroxyethyl starch (HES) in a plasma-adapted solution is supposed to improve safety with regard to coagulation. The influence of a new plasma-adapted HES preparation on coagulation was studied. Operator-blinded, randomized study. Laboratory in vitro study. Fifteen healthy young men scheduled for blood donation. Blood was diluted by 10%, 30%, and 50% using either a plasma-adapted or nonplasma-adapted (prepared in saline solution) potato-derived 6% HES 130/0.42. Only the composition of the solvent of the 2 HES preparations was different. Rotation thromboelastometry (ROTEM; Pentapharm, Munich, Germany) was used to assess changes in coagulation; whole blood aggregometry with 3 inducers was used to assess effects of dilution with HES on platelet function. Clotting time (CT) and clot formation time were significantly prolonged by 30% and 50% dilution, showing significantly longer times in the non-plasma-adapted than in the plasma-adapted HES group (eg, intrinsic CT at the 30% dilution level: plasma-adapted HES 228 +/- 26 seconds [within normal range] v 269 +/- 29 seconds in the nonplasma-adapted HES group). Clot strengthening and clot firmness were significantly reduced by the non-plasma-adapted HES at the 30% dilution level. Platelet aggregation was significantly more reduced by the non-plasma-adapted HES at the 30% and 50% dilution levels. Dilution with the nonplasma-adapted HES 130/0.42 was associated with more negative effects on thromboelastometry and platelet aggregation than the same HES 130/0.4 dissolved in a plasma-adapted solution. The benefits of using a plasma-adapted modern HES preparation on blood loss and use of blood/blood products in cardiac surgery need to be studied.


[Relationship between changes of endogenous nitric oxide synthase inhibitor and hydrolase and initiation of pre-eclampsia].
To investigate the role of dimethylarginine dimethylaminohydrolase-2 (DDAH-2)/asymmetric dimethylarginine (ADMA) in pathophiology of preeclampsia by detecting expression of DDAH-2 in placenta and serum plasma ADMA. From Jan. 2004 to Jan. 2005, 30 preeclampsia patients (PE group) were chosen in the Third Affiliated Hospital, Guangzhou Medical College matched with 10 normal third trimester women as control (control group). The placental DDAH-2 mRNA expression was detected by fluorescence quantitative polymerase chain reaction (FQ-PCR) and the plasma concentration of ADMA was determined by high performance liquid chromatography (HPLC). (1) The level of ADMA in PE group was significantly higher that than of control group [(18.0 +/- 7.2) mg/L vs. (10.3 +/- 1.7) mg/L, P < 0.01]. The expression level of ADMA in preeclampsia occurring before 34 gestatinal weeks was significantly higher than that of preeclampsia occurring after 34 gestational weeks [(22.0 +/- 7.0) mg/L vs. (12.7 +/- 2.8) mg/L, P < 0.01]. (2) The Placental DDAH-2 mRNA expression in preeclampsia patients was remarkably lower than that of control group [1 x 10((5.23 +/- 0.45)) copy/microl vs. 1 x 10((5.65 +/- 0.08)) copy/microl, P < 0.01]. The Placental DDAH-2 mRNA in preeclampsia occurring before 34 gestatinal weeks was significantly lower than that of preeclampsia occurring after 34 gestational weeks [1 x 10((5.02 +/- 0.46)) copy/microl vs. 1 x 10((5.61 +/- 0.19)) copy/microl, P < 0.01]. Our results suggested that low expression of DDAH-2 in placenta and increased serum ADMA level might confer the susceptibility to preeclampsia.


Modeling of steroid estrogen contamination in UK and South Australian rivers predicts modest increases in concentrations in the future.
The prediction of risks posed by pharmaceuticals and personal care products in the aquatic environment now and in the future is one of the top 20 research questions regarding these contaminants following growing concern for their biological effects on fish and other animals. To this end it is important that areas experiencing the greatest risk are identified, particularly in countries experiencing water stress, where dilution of pollutants entering river networks is more limited. This study is the first to use hydrological models to estimate concentrations of pharmaceutical and natural steroid estrogens in a water stressed catchment in South Australia alongside a UK catchment and to forecast their concentrations in 2050 based on demographic and climate change predictions. The results show that despite their differing climates and demographics, modeled concentrations of steroid estrogens in effluents from Australian sewage treatment works and a receiving river were predicted (simulated) to be similar to those observed in the UK and Europe, exceeding the combined estradiol equivalent's predicted no effect concentration for feminization in wild fish. Furthermore, by 2050 a moderate increase in estrogenic contamination and the potential risk to wildlife was predicted with up to a 2-fold rise in concentrations.


Exertion during uphill, level and downhill walking with and without hiking poles.
This study examined the effects of poles when walking on the rate of perceived exertion (RPE), physiological and kinematics parameters, and upon the mean ratio between locomotor and respiratory rhythms. Twelve healthy male and female volunteers, aged 22 to 49 years old, completed on a motorized treadmill in a counterbalanced randomized order 12 walking trials for 10 min at an individually preferred walking speed, with three grades (horizontal level, uphill or downhill with a slope of 15%), with and without hiking poles and a load carriage of 15% of body mass. During all testing sessions, heart rate (HR), oxygen consumption (VO2), ventilation (VE), tidal volume (VT), breathing frequency (Bf), and stride frequency were recorded continuously during the last 5-min of each trial. At the end of each trial, subjects were asked to give RPE. Energy cost (EC) and VE increased significantly with the grade (-15% < 0% < +15%) and with the carrying load. VT was significantly less important with hiking poles, while Bf was significantly more elevated. VO2 and EC increased (p < 0.05) with the use of the hiking poles only during the downhill trials. No significant effect of poles was observed on HR, RPE, and preferred walking speed. The average ratio between the locomotor and respiratory frequencies was significantly influenced by the three experimental factors tested. There was a significant relationship between average ratio of leg movement per breath and EC of walking among all conditions (r = 0.83, n = 12). These results suggest that the use of the hiking poles had a significant influence on the respiratory and energetic responses only during downhill walking. Key pointsEnergetic cost, respiratory responses, stride rate, respiratory to cycle rate ratio were significantly influenced by the use of hiking poles according to the grade at self-selected walking speed.Hiking poles induced an increase in respiratory frequency, VE and energetic cost during downhill, while little changes were observed during level and uphill terrain.The original results obtained in downhill necessitate supplementary studies in the field in order to confirm these first tendencies on treadmill.


Repeated exposure to methamphetamine, cocaine or morphine induces augmentation of dopamine release in rat mesocorticolimbic slice co-cultures.
Repeated intermittent exposure to psychostimulants and morphine leads to progressive augmentation of its locomotor activating effects in rodents. Accumulating evidence suggests the critical involvement of the mesocorticolimbic dopaminergic neurons, which project from the ventral tegmental area to the nucleus accumbens and the medial prefrontal cortex, in the behavioral sensitization. Here, we examined the acute and chronic effects of psychostimulants and morphine on dopamine release in a reconstructed mesocorticolimbic system comprised of a rat triple organotypic slice co-culture of the ventral tegmental area, nucleus accumbens and medial prefrontal cortex regions. Tyrosine hydroxylase-positive cell bodies were localized in the ventral tegmental area, and their neurites projected to the nucleus accumbens and medial prefrontal cortex regions. Acute treatment with methamphetamine (0.1-1000 µM), cocaine (0.1-300 µM) or morphine (0.1-100 µM) for 30 min increased extracellular dopamine levels in a concentration-dependent manner, while 3,4-methylenedioxyamphetamine (0.1-1000 µM) had little effect. Following repeated exposure to methamphetamine (10 µM) for 30 min every day for 6 days, the dopamine release gradually increased during the 30-min treatment. The augmentation of dopamine release was maintained even after the withdrawal of methamphetamine for 7 days. Similar augmentation was observed by repeated exposure to cocaine (1-300 µM) or morphine (10 and 100 µM). Furthermore, methamphetamine-induced augmentation of dopamine release was prevented by an NMDA receptor antagonist, MK-801 (10 µM), and was not observed in double slice co-cultures that excluded the medial prefrontal cortex slice. These results suggest that repeated psychostimulant- or morphine-induced augmentation of dopamine release, i.e. dopaminergic sensitization, was reproduced in a rat triple organotypic slice co-cultures. In addition, the slice co-culture system revealed that the NMDA receptors and the medial prefrontal cortex play an essential role in the dopaminergic sensitization. This in vitro sensitization model provides a unique approach for studying mechanisms underlying behavioral sensitization to drugs of abuse.


Use of imatinib mesylate in elderly patients in Northern Ireland: evidence of comparable haematological and molecular responses to younger patients.
Advanced age is an indicator of poor prognosis in chronic myeloid leukaemia (CML). Since obtaining its UK licence in 2001, the tyrosine kinase inhibitor imatinib mesylate has effected a paradigm shift in the treatment of CML. We compared survival and molecular response rates in elderly patients to younger patients presenting with CML since the introduction of imatinib. Twenty-five patients aged >60 years were identified. No significant survival difference was found when this group was compared with younger patients. In the elderly group, 53% of those with molecular data (36% of all elderly patients) had a major molecular response as assessed by real time quantitative PCR (RT-PCR). The advent of imatinib therapy appears to have ameliorated much of the negative impact of advancing age on survival in patients with CML.


Teaching the Evaluation of Female Pelvic Pain: A Hands-On Simulation to Reinforce Exam Skills and Introduce Transvaginal Ultrasound.
Reproductive-age female patients commonly seek evaluation for pelvic pain in a variety of health care settings. Thus, teaching medical students how to effectively evaluate female pelvic pain is a necessary part of medical education. There are limited opportunities, however, to reinforce the needed skills for this common but sensitive presentation that can be anxiety-producing for preclinical students. The case involved a 23-year-old female presenting with lower abdominal/pelvic pain. Students performed the necessary history, physical examination, cervical sampling, and transvaginal ultrasound evaluation to make the diagnosis of pelvic inflammatory disease (PID) complicated by a tubo-ovarian abscess. The 30-minute simulated patient encounter was followed by a 30-40 minute faculty-led debrief. This simulation case has been sustained in the curriculum since 2011 for 65 students per year. Through use of a faculty critical action checklist, debrief discussion, examination performance, and student evaluation feedback, this simulation has demonstrated effectiveness. Of students, 93 of 193 students (48%) who participated in the simulation case from 2018-2020 completed a survey in which they rated the degree of agreement with statements about the simulation based on a 5-point Likert Scale (1 = strongly disagree, 5 = strongly agree). All questions had a mean response of 4.5-4.8 in 2018-2020, demonstrating the consistent agreement by students of the clarity, fidelity, and knowledge-enhancing value of the simulation. This simulation provided a useful opportunity and a safe environment for preclinical medical students to acquire knowledge and skills necessary to evaluate a female patient with pelvic pain and PID.


Age-adjusted exact trend tests in the event of rare occurrences.
Preclinical animal carcinogenicity studies are usually concerned with testing the statistical significance of a dose-response relationship. When the response consists of a rare event such as the development of a certain type of tumor, exact statistical methods are often employed. The exact randomization trend test based on the multivariate hypergeometric distribution is less powerful in the presence of treatment-related risks other than the specified response. Particularly, the loss of power becomes more pronounced when competing risks cause progressively higher mortality rates with increasing dose, which is usual in practice. An age-adjusted form of the randomization test is proposed to adjust for this effect. Permutational distribution for Peto's cause-of-death (COD) test is also explored and compared with its asymptotic counterpart by simulation. The use of COD information has been a controversial issue due to the subjectivity in the pathologists' determinations as well as for economic reasons. The proposed age-adjusted exact test does not require COD, and it is shown to compare favorably to the COD tests via an extensive Monte Carlo simulation. Applications of the methods to two real data sets are included.


Kinetic boundary conditions in the lattice Boltzmann method.
Derivation of the lattice Boltzmann method from the continuous kinetic theory [X. He and L. S. Luo, Phys. Rev. E 55, R6333 (1997); X. Shan and X. He, Phys. Rev. Lett. 80, 65 (1998)] is extended in order to obtain boundary conditions for the method. For the model of a diffusively reflecting moving solid wall, the boundary condition for the discrete set of velocities is derived, and the error of the discretization is estimated. Numerical results are presented which demonstrate convergence to the hydrodynamic limit. In particular, the Knudsen layer in the Kramers' problem is reproduced correctly for small Knudsen numbers.


Correction of coronal suture synostosis using suture and dura mater allografts in rabbits with familial craniosynostosis.
Resynostosis following surgical correction of craniosynostosis is a common clinical correlate. Recent studies suggest that the dura mater is necessary to maintain suture patency. It has also been hypothesized that dura mater from synostotic individuals may provide aberrant biochemical signals to the osteogenic fronts of the calvaria, which result in premature suture fusion and subsequent resynostosis following surgery. This study was designed to test this hypothesis by surgically manipulating the coronal suture and dura mater in rabbits with familial craniosynostosis to prevent postsurgical resynostosis. Craniofacial growth and histomorphometric data were collected from 129 rabbits: 72 normal controls and 57 rabbits with bilateral coronal suture synostosis (15 unoperated on controls; 13 surgical controls; 9 dura mater transplant only; 10 suture transplant only; and 10 suture and dura mater transplant). At 10 days of age, all rabbits had radiopaque amalgam markers placed on either side of the coronal, frontonasal, and anterior lambdoidal sutures. At 25 days of age, 42 synostosed rabbits had a 3 to 5-mm wide coronal suturectomy. Coronal sutures and/or underlying dura mater allografts were harvested from same-aged, wild-type, isohistogenic control rabbits and transplanted onto the dura mater of synostosed host rabbits. Serial radiographs were taken at 10, 25, 42, and 84 days of age, and the suturectomy sites were harvested at 84 days of age in 44 rabbits and serially sectioned for histomorphometric examination. Results revealed that cranial vault growth was significantly (p < .05) improved following surgical release of the fused coronal suture compared with synostosed rabbits who were not operated on but was still significantly different (p < .05) from that of normal control rabbits. By 84 days of age, significant (p < .05) differences were noted in calvarial suture marker separation, cranial vault shape indices, and cranial base angles between rabbits with and without dura mater allografts, probably as a result of resynostosis of the suturectomy site or suture-only allografts. Qualitative histological examination revealed that at 84 days of age rabbits with suture and dura allografts had patent coronal sutures, suture-only allografts had fused coronal sutures with extensive endosteal hyperostosis, dura mater-only allografts had some new bone in the suturectomy site that resembled rudimentary osteogenic fronts, and suturectomy controls had extensive endosteal bone formation and resynostosis of the suturectomy site. Significantly (p < .05) more bone was found in the suturectomy sites of rabbits without dura mater allografts compared with rabbits with dura mater allografts. Results support the initial hypothesis that normal dura mater allografts will maintain suture or suturectomy site patency and allow unrestricted craniofacial growth. However, it is still unclear whether the dura mater from normal rabbits was providing biochemical signals to the transplanted sutures or suturectomy sites or simply acting as a barrier to prevent abnormal biochemical signals from the dura mater of synostosed rabbits from reaching the calvaria. The clinical and therapeutic implications of these procedures are discussed.


Deletion of Asn281 in the alpha-subunit of the human insulin receptor causes constitutive activation of the receptor and insulin desensitization.
We studied the structure and function of the insulin receptor (IR) in two sisters with leprechaunism. The patients had inherited alterations in the IR gene and were compound heterozygotes. Their paternal IR allele carried a major deletion, including exons 10-13, which shifted the reading frame and introduced a premature chain termination codon in the IR sequence. This allele was expressed at a very low level in cultured fibroblasts (< 10% of total IR messenger ribonucleic acid content) and encoded a truncated protein lacking transmembrane and tyrosine kinase domains. The maternal IR allele was deleted of 3 bp in exon 3, causing the loss of Asn281 in the alpha-subunit. This allele generated levels of IR messenger ribonucleic acid and cell surface receptors similar to those seen in control fibroblasts. However, IRs from patients' cells had impaired insulin binding and exhibited in vivo and in vitro constitutive activation of autophosphorylation and tyrosine kinase activity. As a result of this IR-preactivated state, the cells were desensitized to insulin stimulation of glycogen and DNA syntheses. These findings strongly suggest that Asn281 of the IR alpha-subunit plays a critical role in the inhibitory constraint exerted by the extracellular alpha-subunit over the intracellular kinase activity.


Is this a bridge too far?
Maeda et al. present what may be the second reported case of transcatheter aortic valve replacement (TAVR) followed by staged open surgical aortic valve replacement (SAVR) in a high-risk patient. The authors propose that TAVR may serve as a bridge procedure before SAVR for aortic stenosis in selected younger patients with high surgical risk. Further experience may clarify how long to wait after TAVR to perform SAVR. Timing will be a balance between improving surgical risk versus increasing difficulty removing the prosthesis. Knowledge of TAVR durability will ultimately be needed to decide between "destination" TAVR versus bridging to SAVR with a more durable device.


Incidence of left ventricular hypertrophy in children with kidney disease: impact of method of indexation of left ventricular mass.
Patients with chronic kidney disease are at high risk of cardiovascular morbidity and mortality. Increased left ventricular mass (LVM) has been shown to be an adverse prognostic factor. LVM may be indexed for body size by different methods related to height, weight, or body surface area (BSA). Our Null hypothesis was that different methods of indexation would not influence categorization as to whether LVM was within normal limits or increased. Prospective study in children with renal disease. M-mode echocardiography assessed by single investigator blinded to medical therapy. Three different partition values and two different published z-scores were used: Method 1: indexation of LVM to the allometric height in metres raised to the power of 2.7 (m(2.7)), value of 38.6 g/m(2.7) denotes 95th percentile. Method 2: indexation of LVM by body weight, ratio of LVM in gm/kg of >3.0 indicating LVH. Method 3: indexation by BSA, 88.9 g/m(2) represents 95th percentile. Z-score based methods from recent studies with z-score >1.65 denoting LVH, Method 4: z-score indexed either for BSA or Method 5, z-score indexed for height(2.7). One hundred and twenty-three echocardiograms were performed in 80 patients with a mean +/- SD age of 13.1 +/- 3.1 years, height 147.2 +/- 15.3 cm, weight 46.4 +/- 15.8 kg, and body mass index 20.8 +/- 4.1 kg/m(2). Method 1, LVH was observed in 68 (55.3%) studies. Method 2, 32 (26%) studies had LVM/kg >3.0. Method 3, 51 studies (41.5%) demonstrated LVH. Method 4, 22 (17.9%) studies demonstrated LVH and Method 5, 25 studies (20%) demonstrated LVH (chi(2) test, P < 0.001). Different methods of indexation have a profound influence on the categorization of children with respect to LVH. This will have a major impact on the number of patients who are treated as per current guidelines especially in high-risk groups.


Xanthine oxidase and aldehyde oxidase: a simple procedure for the simultaneous purification from rat liver.
Aldehyde oxidase (AO) and xanthine oxidase (XO) are cytosolic enzymes that have been involved in some pathological conditions and play an important role in the biotransformation of drugs and xenobiotics. The increasing interest in these enzymes demands for a simple and rapid procedure for their purification. This paper describes for the first time a method that allows simultaneous purification of both enzymes from the same batch of rat livers. It involves few steps, is reproducible and offers high enzyme yields with high specific activities. The rat liver homogenate was fractionated by heat denaturation and by ammonium sulphate precipitation to give a crude extract containing both enzymes. This extract was chromatographed on an Hydroxyapatite column that completely separated AO from XO. Further purification of XO by anion exchange chromatography on a Q-Sepharose Fast Flow column resulted in a highly purified (1200-fold) preparation, with a specific activity of 3.64 U/mg and with a 20% yield. AO was purified about 1000-fold at a yield of 15%, with a specific activity of 3.48 U/mg, by affinity chromatography on Benzamidine-Sepharose 6B. The purified enzymes gave single bands of approximately 300 kDa on a polyacrylamide gel gradient electrophoresis and displayed the characteristic absorption spectra of highly purified enzymes.


Genetic aspects of rheumatoid arthritis.
Studies on the population of patients with rheumatoid arthritis and families with multiple cases of rheumatoid arthritis have provided definite evidence that susceptibility to the disease is determined both by genetic factors associated with alleles of the major histocompatibility complex as well as environmental factors. The development of seropositive, but not seronegative rheumatoid arthritis is associated with the presence in an individual of the Ia alloantigen HLA-DR4. This association is common to all major ethnic groups. Some evidence exists that this association is stronger in patients that have more severe disease but this fact requires further study. The fraction of the seropositive patients with rheumatoid arthritis that lack HLA-DR4 has not been well characterized. The occurrence of certain untoward side effects of therapy is influenced by the presence of HLA-DR2 or HLA-DR3. Family studies emphasize the association with HLA-DR4, and indicate that the disease has a dominant mode of inheritance with partial penetrance. The inheritance of susceptibility appeared, at least in some families, to be primarily associated with the inheritance of HLA-DR4 itself and not well explained by a hypothetical disease susceptibility gene present at low frequency and associated in linkage disequilibrium with a HLA-DR4 marker. However, in others different mechanisms appeared more likely. A model of two MHC genes involved in influencing disease susceptibility is postulated. Speculations concerning the primary disease mechanism are presented involving abnormalities of IR genes, general immune regulation, and factors outside of the immune system.


Turning the Curve Into Straight: Phenogenetics of the Spine Morphology and Coordinate Maintenance in the Zebrafish.
The vertebral column, or spine, provides mechanical support and determines body axis posture and motion. The most common malformation altering spine morphology and function is adolescent idiopathic scoliosis (AIS), a three-dimensional spinal deformity that affects approximately 4% of the population worldwide. Due to AIS genetic heterogenicity and the lack of suitable animal models for its study, the etiology of this condition remains unclear, thus limiting treatment options. We here review current advances in zebrafish phenogenetics concerning AIS-like models and highlight the recently discovered biological processes leading to spine malformations. First, we focus on gene functions and phenotypes controlling critical aspects of postembryonic aspects that prime in spine architecture development and straightening. Second, we summarize how primary cilia assembly and biomechanical stimulus transduction, cerebrospinal fluid components and flow driven by motile cilia have been implicated in the pathogenesis of AIS-like phenotypes. Third, we highlight the inflammatory responses associated with scoliosis. We finally discuss recent innovations and methodologies for morphometrically characterize and analyze the zebrafish spine. Ongoing phenotyping projects are expected to identify novel and unprecedented postembryonic gene functions controlling spine morphology and mutant models of AIS. Importantly, imaging and gene editing technologies are allowing deep phenotyping studies in the zebrafish, opening new experimental paradigms in the morphometric and three-dimensional assessment of spinal malformations. In the future, fully elucidating the phenogenetic underpinnings of AIS etiology in zebrafish and humans will undoubtedly lead to innovative pharmacological treatments against spinal deformities.


Visual performance in night-time driving conditions.
This paper introduces an experimental multitechnique method which was developed to establish a basis for a task performance-based mesopic photometry. This approach considers night-time driving by dividing visual performance into three visual tasks, of which achromatic threshold and reaction time are presented. The performance of both visual tasks decreased with decreasing luminance level from 1 to 0.01 cd m(-2), showing the strong effect of light level on visual performance in driving. The behaviour of the achromatic contrast threshold and reaction time for low-contrast targets was similar in terms of spectral effects, the strongest effects occurring at the lower mesopic levels. Both measures showed the Purkinje shift with decreasing luminance levels. The experimental data were used to calculate mesopic performance measures with the new mesopic model. The results imply that compared with V(lambda), spectral sensitivity in night-time driving can be better described with a mesopic model based on visual performance measures.


Effect of culture systems on mouse early embryo development.
The amount of oxygen available to embryos in drop cultures under paraffin may be limited by the gas mixture employed, the method of equilibration or by the use of positive or negative pressure filtration. When these factors were varied, in experiments using Swiss outbred (SO) embryos, the only significant difference detected was the poorer development of embryos from the 1-cell to blastocyst stage when cultured in medium without prior equilibration. Also under these conditions, the inclusion of glucose in the medium did not increase the incidence of 2-cell block, and glutamine in the presence of glucose enhanced the development of 1-cell embryos to blastocysts. One-cell (C57BL/6 x SJL) F1 x SO embryos were successfully cultured in HEPES buffered CZB medium with added bicarbonate, under an atmosphere of air. The proportion of blastocysts formed in this medium, with a concentration of 10 mM sodium bicarbonate, was not different from that developed in CZB under 5% CO2 in air.


3D anatomical variations of hepatic vasculature and bile duct for right lateral sector of liver with special reference to transplantation.
To achieve a safer living related liver transplantation (LRLT) using the right lateral sector, anatomical variations of the portal vein, hepatic artery and bile duct for the right lateral sector and their three dimentional (3D) relationship were assessed by integrated 3D-CT images. 52 patients who underwent contrast enhanced multi-detector row CT (MD-CT) and MD-CT cholangiography were enrolled. Data from contrast enhanced MD-CT were used to reconstruct the 3D images of the hepatic artery and portal vein. 3D images reconstructed from MD-CT data of the hepatic artery, portal vein and bile duct were integrated into a single image. The dual branching of the right lateral portal vein was observed in 22 (42.3%) patients. Three (5.8%) had dual right lateral ducts and 14 (26.9%) had dual right lateral arteries. Among them, "south-turning" artery and "north-turning" bile duct was observed in 22 (42.3%). "South-turning" artery and "south-turning" bile duct were 3 (5.8%). "North-turning" artery and "north-turning" bile duct were 2 (7.4%). Only 27 (51.9%) had single portal vein, bile duct and artery for the right lateral sector, those were preferable as candidates for right lateral sector graft transplantation. 3D anatomical variations of portal vein, artery and bile duct for the right lateral sector were complexed, and only half of the donor candidates had preferable hepatic structures for right lateral sector graft transplantation. Understanding of the 3D hepatic structures by 3D-CT may contribute to a better definition of anatomical contraindications for LRLT which may further results in more safe and widely applied right lateral sector graft LRLT.


Evaluating efficiency of counties in providing diabetes preventive care using data envelopment analysis.
For patients with diabetes, annual preventive care is essential to reduce the risk of complications. Local healthcare resources affect the utilization of diabetes preventive care. Our objectives were to evaluate the relative efficiency of counties in providing diabetes preventive care and explore potential to improve efficiencies. The study setting is public and private healthcare providers in US counties with available data. County-level demographics were extracted from the Area Health Resources File using data from 2010 to 2013, and individual-level information of diabetes preventive service use was obtained from the 2010 Behavioral Risk Factor Surveillance System. 1112 US counties were analyzed. Cluster analysis was used to place counties into three similar groups in terms of economic wellbeing and population characteristics. Group 1 consisted of metropolitan counties with prosperous or comfortable economic levels. Group 2 mostly consisted of non-metropolitan areas between distress and mid-tier levels, while Group 3 were mostly prosperous or comfortable counties in metropolitan areas. We used data enveopement analysis to assess efficiencies within each group. The majority of counties had modest efficiency in providing diabetes preventive care; 36 counties (57.1%), 345 counties (61.1%), and 263 counties (54.3%) were inefficient (efficiency scores < 1) in Group 1, Group 2, and Group 3, respectively. For inefficient counties, foot and eye exams were often identified as sources of inefficiency. Available health professionals in some counties were not fully utilized to provide diabetes preventive care. Identifying benchmarking targets from counties with similar resources can help counties and policy makers develop actionable strategies to improve performance.


[Expression of P33ING1, P53 and their relationship with apoptosis in anal canal carcinoma].
To explore the expressions of P33ING1, P53 and their relationships with apoptosis in anal canal carcinoma (ACC). The expressions of P33ING1, P53 proteins were measured by immunohistochemistry method (SP method), and apoptosis was detected in 42 cases with ACC, 36 cases with anal canal adenoma (ACA) or anal canal papilloma (ACP), and 40 cases with paraanal inflammatory mass(PAIM). The positive expression rates of P33ING1 and P53 proteins were 40.5% (17/42), 97.2% (35/36) and 97.5% (39/40), 50.0% (21/42), 22.2% (8/36) and 27.5% (11/40) respectively, and the average apoptosis indexes(AI) were (10.27+/- 1.23) per thousand, (42.75+/- 0.98) per thousand and (42.67+/- 1.04) per thousand respectively in ACC, ACA or ACP and PAIM. There were significant differences in the positive expression rates of P33ING1, P53 and apoptosis index between ACC and the other two groups respectively (P< 0.05). Among 21 cases of ACC with positive expression of P53 protein,there were 18 cases with P33ING1 negative expression. P33ING1 expression decrease in ACC, which may play an important role in the carcinogenesis and progression of ACC. P33ING1 and P53 may have an synergistic effect of suppressing cell growth and accelerating cell apoptosis.


The migration of persons with AIDS: data from 12 states, 1985 to 1992. AIDS Mortality Project Group.
This study measured the migration of persons with the acquired immunodeficiency virus (AIDS) between diagnosis and death using AIDS case and death reports from 12 states for 1985 to 1992. Of 49,805 persons with AIDS, 10.6% changed their place of residence, and half of these individuals who moved changed their state of residence. Migration had relatively little impact on the numbers of persons with AIDS in the largest metropolitan areas, which accounted for approximately 90% of AIDS diagnoses. Although only 3% of deaths occurred in residents of nonmetropolitan areas, the net effect of migration was a 24% increase in the number of persons with AIDS residing in such areas.


Mast cell sarcoma: new cases and literature review.
Mast cell sarcoma (MCS) is a rare form of mastocytosis characterized by the presence of solid tumor(s) comprising malignant mast cells that harbor destructive infiltration capability and metastatic potential. Here, we present an extensive literature review and report on 23 cases of MCS, including 3 new cases from the French National Reference Center for Mastocytosis. From our analysis, it appears that MCS can occur at any age. It can manifest de novo or, to a lesser extent, may evolve from a previously established mastocytosis. Bone tumor is a frequent manifestation, and symptoms of mast cell activation are rare. Histological diagnosis can be difficult because MCS is frequently composed of highly atypical neoplastic mast cells and can thus mimic other tumors. Unexpectedly, the canonical KIT D816V mutation is found in only 21% of MCS; therefore, complete KIT gene sequencing is required. The prognosis of patients with MCS is poor, with a median survival time of less than 18 months, and progression to mast cell leukemia is not unusual. Because conventional chemotherapies usually fail, the role of targeted therapies and bone marrow transplantation warrants further investigation in such aggressive neoplasms.


Melancholia: definitions, risk factors, personality, neuroendocrine markers and differential antidepressant response.
To evaluate the CORE measure of melancholia, against the DSM-IV construct of melancholia. To evaluate the validity of both the CORE and DSM-IV constructs of melancholia against psychosocial risk factors, anxiety and personality disorder comorbidity, neuroendocrine markers and differential anti depressant response to fluoxetine and nortriptyline. One hundred and ninety-five outpatients with major depression were evaluated for melancholia with both the DSM-IV criteria and the CORE evaluation. Both constructs were evaluated for validity against psychosocial risk factors, comorbidity, biological markers and differential antidepressant response. The CORE measure has satisfactory interrater reliability when used dimensionally, but has unacceptably low agreement for making a categorical diagnosis of melancholia. There is remarkably poor agreement (kappa = 0.11) between the CORE and DSM-IV criteria for melancholia. Neither the DSM-IV nor CORE criteria for melancholia identified subgroups of patients with better childhood environments or less anxiety or personality disorder comorbidity. The CORE criteria for melancholia, but not DSM-IV, identified patients with neuroendocrine disturbance. CORE scores also were associated with differential responses to fluoxetine and nortriptyline, but not in anticipated directions. Thus, high CORE scores were associated with a higher recovery rate with fluoxetine than nortriptyline. While the episode specifier of melancholia should be retained in diagnostic systems, the DSM-IV criteria were not validated against any of the variables examined in this study. The CORE construct of melancholia, was validated against neuroendocrine measures, and was associated with a differential antidepressant response. However, the limits imposed by interrater reliability,suggest the CORE measure should be used dimensionally and not to make a categorical diagnosis of melancholia.


1-Benzyl-1,2,3,4-tetrahydro-β-carboline as channel blocker of N-methyl-D-aspartate receptors.
N-methyl-d-aspartate (NMDA) receptors belong to the family of ligand-gated ion channels and are important for synaptic plasticity and memory function. The NMDA receptor consists of a voltage-dependent channel permeable to Ca(2+) and Na(+) . In Alzheimer's disease, neuronal degeneration is thought to cause an excessive release of glutamate to the extracellular space, which may in turn mediate prolonged stimulation of the NMDA receptor complex and, as a consequence, excessive calcium influx into neuronal cells, leading to subsequent cell death. This process is called glutamate-induced excitotoxicity, and its inhibition may present an effective antidementive therapy. We found that 1-benzyl-1,2,3,4-tetrahydro-β-carboline (1a) blocked NMDA receptor-mediated, glutamate-induced excitotoxicity with an IC(50) value of 27.4 μm, whereas the closely related 1-phenyl-1,2,3,4-tetrahydro-β-carboline (1b) had no effect. The binding modes of the reported compounds were studied by in silico docking simulations. We demonstrate that compounds (S)-1a and (R)-1a, but not (S)-1b and (R)-1b, have the same characteristics of potent NMDA receptor blockers, because they establish the main interactions inside the vestibule region of the receptor described previously for the high-affinity NMDA receptor blocker, MK-801.


Theoretical Study of [2 + 1] cycloaddition of CO and CS to acetylenes forming cyclopropenones and cyclopropenethiones.
The [2 + 1] cycloadditions of carbon monoxide and carbon monothioxide CX (X = O, S) to acetylenes (R1C triple bond CR2 with R1 = H, OH and R2 = CH3, OH, NH2, C6H5) have been studied at the B3LYP/6-311G(d,p) level. It has been shown that the reaction proceeds in two steps forming first an intermediate having the properties of both a carbene and a zwitterion followed by a ring closure leading to cyclopropenones or cyclopropenethiones. The solvent effect does not play an important role in the course of the cycloaddition. The estimation of the first vertical excitation energies by CIS and TD-B3LYP methods shows that the reactions likely take place in the ground state rather than in an excited state. All the studied cyclopropenones and cyclopropenethiones are aromatic as shown by their NICS values and confirmed by calculated and experimental NMR chemical shifts. Different reactivity criteria including HOMO coefficient, local softness, hardness, polarizability, and NICS are used to predict the site selectivity in all studied cases, and the NICS criterion seems to yield the best results among them.


Assessing the acceptability of village health workers' roles in improving maternal health care in Gombe State, Nigeria a qualitative exploration from women beneficiaries.
Maternal, and under-five mortality rates in Gombe State are disproportionately high. The Society for Family Health (a Non-Governmental Organization) in collaboration with Gombe State Primary Health Care Development Agency implemented the Village Health Worker (VHW) Program in Gombe to address the low uptakes of maternal neonatal and child health (MNCH) services and reduced the impact of healthcare worker insufficiency. VHWs are lay indigenous women trained to educate and encourage women to use MNCH services, provide simple community-based maternal and new-born care through home visits, and facilitate facility linkage. We assessed the acceptability of VHW services among women beneficiaries of the Program. Qualitative data were obtained through six focus group discussions with 58 women beneficiaries of the VHW program who delivered within the last 12 months preceding study period (October-November 2018). Themes explored were roles and acceptability of VHWs, and the influence of VHWs on the uptake of MNCH services. We analyzed data with NVivo 12, using Grounded Theory. Participants' mean age was 25.1 (± 5.3) years old. Most participants 39 (67%), had been in contact with a VHW for at least 10 months. VHWs visited pregnant women at home and registered them for antenatal care, provided them basic maternal healthcare, health education, and facilitated facility linkage. Participants generally accepted the VHW Program because it was community-based, VHWs were indigenous community members, delivered clear messages, and influenced husbands and mothers-in-law to support women's' use of MNCH services. VHWs' interventions were perceived to have improved health literacy and the uptake of MNCH services. Participants generally admired the VHW occupation and recommended VHW program scale-up, and for VHWs to be offered basic obstetric training and employment by health facilities or the government. The general acceptance and positive views of VHWs from beneficiaries of the program demonstrates the feasibility of the program to improve the uptake of MNCH services.


Influence of benomyl and prometryn on the soil microbial activities and community structures in pasture grasslands of Slovakia.
The effects of pesticides (a herbicide and a fungicide) on the microbial community structure and their activity were analyzed in soil from four alpine pasture grasslands in Slovakia. Specifically, the effects of the herbicide, Gesagard (prometryn active ingredient), and fungicide, Fundazol 50 WP (benomyl active ingredient), on the microbial respiration activity (CO2 production), the numbers of selective microbial physiological groups (CFU.g(-1)) and the structure (relative abundance) of soil microbial communities [(phospholipid fatty acid (PLFA)] were analyzed under controlled laboratory conditions. All treatments including the treatments with pesticides increased (statistically significantly) the production of CO2 in all fields during 21 days of incubation and posed a statistically insignificant negative influence on the numbers of the observed physiological groups of microorganisms. The significantly negative influence was evaluated only in the numbers of two physiological groups; spores of bacteria utilizing organic nitrogen and bacteria, and their spores utilizing inorganic nitrogen. A shift in the microbial composition was evident when the PLFA patterns of samples from different sites and treatments were compared by the Principal Component Analysis (PCA). According to the second component PCA 2 (15.95 %) the locations were grouped into two clusters. The first one involved the Donovaly and Dubakovo sites and the second one contained the Velka Fatra and Mala Fatra locations. The PLFA composition of the soils showed important changes after the treatment with pesticides according to PCA 1 (66.06 %). Other treatments had not had a significant effect on the soil microbial community with the exception of the population of fungi. The lower relative abundance (significant effect) of Gram-positive bacteria, actinomycetes and general group of bacteria were determined in samples treated by the herbicide Gesagard. The application of fungicide Fundazol decreased (statistically significantly) the relative abundance of actinomycetes and general group of bacteria and paradoxically increased the population of fungi.


Factors affecting sexual functioning of women in the mid-life years.
To model the interaction of hormones, symptoms and psychosocial factors on women's sexuality during the menopausal transition. A prospective, observational study was carried out of a community-based sample of 438 Australian-born women aged 45-55 years at baseline. The study comprised six annual assessments in the women's own homes utilizing a core questionnaire, with rating scales for well-being and daily hassles, and a Personal Experiences Questionnaire as a measure of sexual functioning. Levels of follicle stimulating hormone (FSH), estradiol and inhibin were measured annually. Statistical analysis was performed by structural equation modelling. The retention rate was 90% (final sample size after exclusions, n = 354). The normal fit index for the global model obtained was 0.92. There is a significant direct effect of menopausal status on vaginal dryness/dyspareunia, and an indirect effect on sexual responsivity via a direct effect of menopausal status on symptoms, which then affect well-being. Menopausal status reflects hormonal status. Feelings for the partner and the partner's sexual problems have direct effects on different aspects of sexual functioning. Other social variables such as paid work, interpersonal stress, daily hassles and educational level affect sexual functioning indirectly via effects on symptoms and well-being. Psychosocial factors, symptoms and the menopausal transition affect women's sexual functioning during the mid-life years.


Posttranscriptional regulation of EcoP1I and EcoP15I restriction activity.
Efficient establishment of a DNA restriction-modification (R-M) system in a non-modified cell requires a tight control of the potentially lethal activity of the restriction enzyme. The type III R-M systems EcoP1I and EcoP15I can be transferred to non-modified Escherichia coli cells by transfection, conjugation or transformation and become established without difficulty. Modification activity is expressed immediately after the R-M genes enter the cell, whereas the expression of restriction activity is delayed until complete protection of the cellular DNA is achieved by methylation. We have shown by Western blot analysis that the expression of the modification polypeptide subunit positively regulates the amount of restriction subunit present in the cell. The finding that ribosomal alterations affected the expression of restriction activity pointed to additional control at the translational level. The analysis of EcoP1I expression in E. coli strains mutated in either of the ribosomal proteins S12 (rpsL) or S4 (rpsD) suggests that the level of in vivo restriction activity can be modulated both by a decrease in the efficiency of translation and by varying ribosomal accuracy conditions. In addition, we have preliminary evidence from in vivo gene fusion studies that the res gene may code for more than one gene product.


Toward Sustainable Tackling of Biofouling Implications and Improved Performance of TFC FO Membranes Modified by Ag-MOF Nanorods.
In this work, nanorods with high antibacterial properties were synthesized with silver acetate as the metal source and 2-aminoterephthalic acid as the organic linker and were then embedded into thin-film composite (TFC) membranes to amend their performance as well as to alleviate biofouling. Silver metal-organic framework (Ag-MOF) nanorods with a length smaller than 40 nm were incorporated within the polyamide thin selective layer of the membranes during interfacial polymerization. The interaction of the synthesized nanorods with the polyamide was favored because of the presence of amine-containing functional groups on the nanorod's surface. The results of X-ray photoelectron spectroscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, and atomic force microscopy characterizations proved the presence of Ag-MOF nanorods in the selective layer of thin-film nanocomposite (TFN) membranes. TFN membranes demonstrated improved water permeance, salt selectivity, and superior antibacterial properties. Specifically, the increased hydrophilicity and antibacterial potential of the TFN membranes led to a synergetic effect toward biofouling mitigation. The number of live bacteria attached to the surface of the neat TFC membrane decreased by more than 92% when a low amount of Ag-MOF nanorods (0.2 wt %) was applied. Following contact of the TFN membrane surface with Escherichia coli and Staphylococcus aureus, full inactivation, and degradation of bacteria cells were observed with microscopy, colony-forming unit tests, and disc inhibition zone analyses. This result translated to a negligible amount of the biofilm formed on the active layer. Indeed, the incorporation of Ag-MOF nanorods decreased the metal-ion release rate and therefore provided prolonged antibacterial performance.


Acceptability of a mobile health exercise-based cardiac rehabilitation intervention: a randomized trial.
Mobile technologies (mHealth) have recently been used to deliver behavior change interventions; however, few have investigated the application of mHealth for treatment of ischemic heart disease (IHD). The Heart Exercise And Remote Technologies trial examined the effectiveness of an mHealth intervention to increase exercise behavior in adults with IHD. As a part of this trial, a process evaluation was conducted. One hundred seventy-one adults with IHD were randomized to receive a 6-month mHealth intervention (n = 85) plus usual care or usual care alone (n = 86). The intervention delivered a theory-based, automated package of exercise prescription and behavior change text messages and a supporting Web site. Three sources of data were triangulated to assess intervention participant perceptions: (1) Web site usage statistics; (2) feedback surveys; and (3) semistructured exit interviews. Descriptive information from survey and Web data were merged with qualitative data and analyzed using a semantic thematic approach. At 24 weeks, all intervention participants provided Web usage statistics, 75 completed the feedback survey, and 17 were interviewed. Participants reported reading the text messages (70/75; 93%) and liked the content (55/75; 73%). The program motivated participants to exercise. Several suggestions to improve the program included further tailoring of the content (7/75; 7%) and increased personal contact (10/75; 13%). Adults with IHD were able to use an mHealth program and reported that text messaging is a good way to deliver exercise information. While mHealth is designed to be automated, programs might be improved if content and delivery were tailored to individual needs.


Reduced Brain Gray Matter Volume in Patients With First-Episode Major Depressive Disorder: A Quantitative Meta-Analysis.
Background: The findings of many neuroimaging studies in patients with first-episode major depressive disorder (MDD), and even those of previous meta-analysis, are divergent. To quantitatively integrate these studies, we performed a meta-analysis of gray matter volumes using voxel-based morphometry (VBM). Methods: We performed a comprehensive literature search for relevant studies and traced the references up to May 1, 2021 to select the VBM studies between first-episode MDD and healthy controls (HC). A quantitative meta-analysis of VBM studies on first-episode MDD was performed using the Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) method, which allows a familywise error rate (FWE) correction for multiple comparisons of the results. Meta-regression was used to explore the effects of demographics and clinical characteristics. Results: Nineteen studies, with 22 datasets comprising 619 first-episode MDD and 707 HC, were included. The pooled and subgroup meta-analysis showed robust gray matter reductions in the left insula, the bilateral parahippocampal gyrus extending into the bilateral hippocampus, the right gyrus rectus extending into the right striatum, the right superior frontal gyrus (dorsolateral part), the left superior frontal gyrus (medial part) and the left superior parietal gyrus. Meta-regression analyses showed that higher HDRS scores were significantly more likely to present reduced gray matter volumes in the right amygdala, and the mean age of MDD patients in each study was negatively correlated with reduced gray matter in the left insula. Conclusions: The present meta-analysis revealed that structural abnormalities in the fronto-striatal-limbic and fronto-parietal networks are essential characteristics in first-episode MDD patients, which may become a potential target for clinical intervention.


Heavy metal accumulation of urban domestic rubbish compost in turfgrass by EDTA chelating.
Seven kinds of heavy metal accumulation of rubbish compost in turfgrass by EDTA chelating were investigated. With EDTA application, heavy metal accumulation by two species of turfgrass was increased significantly. The enrichment coefficients of Lolium perenne L(L) and Festuca arundinacea L(F) to Cr reached 9.45 and 6.15 respectively. In the range of EDTA dosages given, heavy metal accumulation in turfgrass increased with increasing EDTA level. There were significant differences in remediation of different metals by applying EDTA. L had high ability to accumulate Cr, Cd, Ni and Zn, showing better remediation to heavy metals of rubbish compost. In contrast, F showed high ability to accumulate Cr, Ni, Cu and Zn. Low EDTA level increased aboveground net primary production (ANP) of turfgrass, but EDTA would considerably inhibit it when EDTA was higher than 20 mmol/kg. The results demonstrated that the optimum dosage of EDTA for remediating heavy metals in rubbish compost by turfgrass was between 10 mmol/kg and 20 mmol/kg.


Effect of insulin-dependent diabetes on plasma lipoproteins in diabetic pregnancy.
A reduction in total plasma cholesterol concentration has been reported in insulin-dependent diabetic (IDDM) pregnant women in early gestation. To determine if this reduction extends throughout gestation and which lipoprotein fractions may be responsible, we measured plasma triglyceride, cholesterol (C), high density lipoprotein cholesterol (HDL-C) and HDL2 and HDL3-C subfractions between 6 and 36 weeks' gestation in normal and IDDM women. Total plasma C was significantly lower in IDDM pregnant subjects between 20 and 36 weeks' gestation as compared to nondiabetic controls, while plasma triglyceride concentrations were not significantly different in this interval. Very low and low density lipoprotein (VLDL, LDL) C concentrations were not statistically significantly different from controls at any of the times studied, while HDL-C was lower throughout diabetic pregnancy as compared to controls, significantly so between 20 and 36 weeks' gestation. The lower HDL-C in IDDM women was associated with a significantly lower HDL3-C level. Plasma apoprotein A-I and A-II concentrations, markers of the HDL2 and HDL3 subclasses, respectively, were measured to corroborate the HDL subfraction changes. Apo A-I and A-II increased significantly between 12 and 28 weeks' gestation in control but not in diabetic pregnant subjects, consistent with a higher HDL3 in normal than in diabetic pregnant subjects. It appears that plasma triglyceride, VLDL and LDL-C, and HDL2-C concentrations are similar in IDDM and normal pregnancy, while total-C, HDL-C and HDL3-C and its associated apoproteins are lower than in normal subjects in late gestation. The mechanism of these changes and their significance for fetal growth and development deserve further study.


Oxidative stress in the pathogenesis of canine zinc-responsive dermatosis.
Zinc deficiency causes skin diseases both in humans and in animals. The underlying pathogenic mechanisms remain unclear, but a growing body of evidence indicates a role for zinc in skin protection against free radical-induced oxidative damage. The immunohistochemical expression of heat shock proteins (HSPs; Hsp27, Hsp72, Hsp73 and Hsp90), Cu/Zn superoxide dismutase (SOD), metallothionein (MT), Ki-67 antigen and active caspase-3 were evaluated in normal canine skin and in samples from eight dogs with zinc-responsive dermatosis. All investigated HSPs showed intense cytoplasmic immunostaining in the affected epidermis. Focal nuclear positivity of Hsp72 was also detected in keratinocytes. Although Cu/Zn SOD expression was similar to that observed in normal skin, MT immunoreactivity occurred in both the cytoplasm and the nucleus of basal cells in normal skin but was absent from the affected epidermis. Caspase-3 activation was also absent in the involved epidermis, which revealed a high Ki-67 index (a 3.5- to 9-fold increase compared with normal skin). These results support the hypothesis that cellular response to stress, particularly oxidative stress, is involved in the pathogenesis of skin lesions in canine zinc-responsive dermatosis. The lack of MT immunoreactivity in the affected epidermis may be indicative of low zinc levels, thus resulting in vulnerability to oxidative damage. In contrast, high expression levels of HSPs in skin during zinc deficiency may confer protection against a variety of dangerous stimuli, contributing to inhibition of apoptosis and to cell cycle regulation of proliferating keratinocytes.


Suite of three protein crystallography beamlines with single superconducting bend magnet as the source.
At the Advanced Light Source, three protein crystallography beamlines have been built that use as a source one of the three 6 T single-pole superconducting bending magnets (superbends) that were recently installed in the ring. The use of such single-pole superconducting bend magnets enables the development of a hard X-ray program on a relatively low-energy 1.9 GeV ring without taking up insertion-device straight sections. The source is of relatively low power but, owing to the small electron beam emittance, it has high brightness. X-ray optics are required to preserve the brightness and to match the illumination requirements for protein crystallography. This was achieved by means of a collimating premirror bent to a plane parabola, a double-crystal monochromator followed by a toroidal mirror that focuses in the horizontal direction with a 2:1 demagnification. This optical arrangement partially balances aberrations from the collimating and toroidal mirrors such that a tight focused spot size is achieved. The optical properties of the beamline are an excellent match to those required by the small protein crystals that are typically measured. The design and performance of these new beamlines are described.


Simultaneous PET/MRI: The future gold standard for characterizing motor neuron disease-A clinico-radiological and neuroscientific perspective.
Neuroimaging assessment of motor neuron disease has turned into a cornerstone of its clinical workup. Amyotrophic lateral sclerosis (ALS), as a paradigmatic motor neuron disease, has been extensively studied by advanced neuroimaging methods, including molecular imaging by MRI and PET, furthering finer and more specific details of the cascade of ALS neurodegeneration and symptoms, facilitated by multicentric studies implementing novel methodologies. With an increase in multimodal neuroimaging data on ALS and an exponential improvement in neuroimaging technology, the need for harmonization of protocols and integration of their respective findings into a consistent model becomes mandatory. Integration of multimodal data into a model of a continuing cascade of functional loss also calls for the best attempt to correlate the different molecular imaging measurements as performed at the shortest inter-modality time intervals possible. As outlined in this perspective article, simultaneous PET/MRI, nowadays available at many neuroimaging research sites, offers the perspective of a one-stop shop for reproducible imaging biomarkers on neuronal damage and has the potential to become the new gold standard for characterizing motor neuron disease from the clinico-radiological and neuroscientific perspectives.


An acceptability study of two pivampicillin mixtures in children in general practice.
In order to evaluate the paediatric patient compliance to treatment with penicillin mixture, 84 children with respiratory system infections were randomized to treatment with pivampicillin (Pondocillin) mixture with two different flavour additives, cocoa-peppermint and banana. Using a scoring system, the taste acceptability and the easiness of administration were evaluated at the beginning and the end of treatment. While taste acceptability and easiness of administration decreased significantly during the treatment (p = 0.046 for taste and p = 0.049 for easiness) with Pondocillin cocoa-peppermint mixture, only small non-significant differences were noticed during treatment with Pondocillin banana mixture.


Right ventricular strain as predictor of pulmonary complications in patients with femur fracture.
Following femur fracture, medullary fat enters the systemic circulation and altered pulmonary haemodynamics may contribute to pulmonary complications. This study evaluated the association between right ventricular (RV) function and pulmonary complications in patients with femur fracture. Patients with a femur fracture who had undergone pre-operative echocardiography that included RV peak global longitudinal strain (RV GLS) were evaluated retrospectively between March 2015 and February 2016. Pulmonary complications were defined as the development of pneumonia or pulmonary thromboembolism during the first postoperative month. Among 78 patients, pulmonary complications developed in eight (10.3%). The RV GLS value of all patients was lower than the normal range. In addition, the RV GLS value of patients with pulmonary complications was significantly lower than that of patients without pulmonary complications. Multivariate regression analyses found that worse RV GLS values independently predicted pulmonary complications [odds ratio (OR) 2.09, 95% confidence interval (CI) 1.047-4.151, p = 0.037]. Receiver operating characteristic curve analysis found that a RV GLS value of -14.85% was the best cut-off value to predict pulmonary complications; sensitivity: 75.0%; specificity: 62.9%. Moreover, patients with RV GLS values > -14.85% had significantly lower pulmonary complication-free survival. In patients with femur fracture, RV GLS values could help predict pulmonary complications. Therefore, patients with RV GLS values > -14.85 should be monitored closely before and after surgery for femur fracture.


[Expression and purification of a novel thermophilic bacterial single-stranded DNA-binding protein and enhancement the synthesis of DNA and cDNA].
Express a novel species of single-stranded DNA-binding protein (SSB) derived from Thermococcus kodakarensis KOD1, abbreviated kod-ssb. And evaluate the effect of kod-ssb on PCR-based DNA amplification and reverse transcription. We express kod-ssb with the Transrtta (DE3), and kod-ssb was purified by affinity chromatography on a Ni2+ Sepharose column, detected by SDS-PAGE. To evaluate the effect of kod-ssb on PCR-based DNA amplification, the human beta globin gene was used as template to amplify a 5-kb, 9-kb and 13-kb. And to detect the effect of kod-ssb on reverse transcription, we used RNA from flu cell culture supernatant extraction as templates to implement qRT-PCR reaction. The plasmid pET11a-kod was transformed into Transetta (DE3) and the recombinant strain Transetta (pET11 a-kod) was obtained. The kod-ssb was highly expressed when the recombinant strain Transetta(pET11a-kod) was induced by IPTG. The specific protein was detected by SDS-PAGE. To confirm that kod-ssb can enhance target DNA synthesis and reduce PCR by-products, 5-, 9-, and 13-kb human beta globin gene fragments were used as templates for PCR. When PCR reactions did not include SSB proteins, the specific PCR product was contaminated with non-specific products. When kod -ssb was added, kod-ssb significantly enhanced amplification of the 5-, 9-and 13-kb target product and minimised the non-specific PCR products. To confirm that kod-ssb can enhance target cDNA synthesis, RNA from flu cell culture supernatant extraction was used as templates for qRT-PCR reaction. The results was that when kod-ssb was added, kod-ssb significantly enhanced the synthesis of cDNA, average Ct value is 19.42, and the average Ct value without kod-ssb is 22.15. kod-ssb may in future be used to enhance DNA and cDNA amplification.


Promoting systematic processing in low-motivation settings: effect of incongruent information on processing and judgment.
Ss received consensus information that was either congruent or incongruent with the valence of persuasive message content. In Experiment 1 Ss believed that their processing task was either important or unimportant whereas in Experiment 2 all Ss believed that their task was unimportant. In accord with the heuristic-systematic model's sufficiency principle, high-task-importance Ss exhibited a great deal of systematic processing regardless of congruency, whereas low-importance Ss processed systematically only when they received incongruent messages; in the congruent conditions heuristic processing dominated. Attitude data generally reflected these processing differences and confirmed the additivity and attenuation assumptions of the model. The utility of the sufficiency principle for understanding motivation for elaborative processing and the relevance of the findings to understanding the processing and judgmental effects of expectancy disconfirmation are discussed.


The course of depression in elderly patients.
Studies on the course of major depressive disorder (MDD) among elderly persons are limited to short periods of follow-up, seldom provide comparisons with younger cohorts, and raise other methodological concerns. Utilizing 15 years of prospective data from the NIMH Collaborative Depression Study, the authors examined the index episode of MDD and the time until first observed recurrence in those who recovered for subjects in four age-groups defined by age at intake: 17-30, 31-50, 51-64, and 65-79 years. Assessments were conducted every 6 months for 5 years and annually thereafter. Survival analysis examined time until recovery and time to first recurrence. Median time-to-recovery was similar for the four groups. Median time-to-first recurrence was significantly shorter for oldest versus the 51-64-year-old group but not the two other groups. The oldest age-group was distinguished from the younger groups by being more likely to be divorced/widowed/separated, to have primary depression, and to have a history of medical illness, particularly cardiovascular disease or cancer. There was no difference in the generally low levels of pharmacotherapy prescribed during the index episode or the subsequent well interval. Elderly patients with MDD may have a greater risk of recurrence than younger individuals. Low levels of treatment characterize the somatic treatment in all the study subjects, regardless of age-group.


PAIP 2019: Liver cancer segmentation challenge.
Pathology Artificial Intelligence Platform (PAIP) is a free research platform in support of pathological artificial intelligence (AI). The main goal of the platform is to construct a high-quality pathology learning data set that will allow greater accessibility. The PAIP Liver Cancer Segmentation Challenge, organized in conjunction with the Medical Image Computing and Computer Assisted Intervention Society (MICCAI 2019), is the first image analysis challenge to apply PAIP datasets. The goal of the challenge was to evaluate new and existing algorithms for automated detection of liver cancer in whole-slide images (WSIs). Additionally, the PAIP of this year attempted to address potential future problems of AI applicability in clinical settings. In the challenge, participants were asked to use analytical data and statistical metrics to evaluate the performance of automated algorithms in two different tasks. The participants were given the two different tasks: Task 1 involved investigating Liver Cancer Segmentation and Task 2 involved investigating Viable Tumor Burden Estimation. There was a strong correlation between high performance of teams on both tasks, in which teams that performed well on Task 1 also performed well on Task 2. After evaluation, we summarized the top 11 team's algorithms. We then gave pathological implications on the easily predicted images for cancer segmentation and the challenging images for viable tumor burden estimation. Out of the 231 participants of the PAIP challenge datasets, a total of 64 were submitted from 28 team participants. The submitted algorithms predicted the automatic segmentation on the liver cancer with WSIs to an accuracy of a score estimation of 0.78. The PAIP challenge was created in an effort to combat the lack of research that has been done to address Liver cancer using digital pathology. It remains unclear of how the applicability of AI algorithms created during the challenge can affect clinical diagnoses. However, the results of this dataset and evaluation metric provided has the potential to aid the development and benchmarking of cancer diagnosis and segmentation.


Genome-Wide Expression Analysis Unravels Fluoroalkane Metabolism in Pseudomonas sp. Strain 273.
Pseudomonas sp. strain 273 grows with medium-chain terminally fluorinated alkanes under oxic conditions, releases fluoride, and synthesizes long-chain fluorofatty acids. To shed light on the genes involved in fluoroalkane metabolism, genome, and transcriptome sequencing of strain 273 grown with 1,10-difluorodecane (DFD), decane, and acetate were performed. Strain 273 harbors three genes encoding putative alkane monooxygenases (AlkB), key enzymes for initiating alkane degradation. Transcripts of alkB-2 were significantly more abundant in both decane- and DFD-grown cells compared to acetate-grown cells, suggesting AlkB-2 catalyzes the attack on terminal CH3 and CH2F groups. Coordinately expressed with alkB-2 was an adjacent gene encoding a fused ferredoxin-ferredoxin reductase (Fd-Fdr). Phylogenetic analysis distinguished AlkB that couples with fused Fd-Fdr reductases from AlkB with alternate architectures. A gene cluster containing an (S)-2-haloacid dehalogenase (had) gene was up-regulated in cells grown with DFD, suggesting a possible role in the removal of the ω-fluorine. Genes involved in long-chain fatty acid biosynthesis were not differentially expressed during growth with acetate, decane, or DFD, suggesting the bacterium's biosynthetic machinery does not discriminate against monofluoro-fatty acid intermediates. The analysis sheds first light on genes and catalysts involved in the microbial metabolism of fluoroalkanes.


Apriori Algorithm for the Data Mining of Global Cyberspace Security Issues for Human Participatory Based on Association Rules.
This study explored the global cyberspace security issues, with the purpose of breaking the stereotype of people's cognition of cyberspace problems, which reflects the relationship between interdependence and association. Based on the Apriori algorithm in association rules, a total of 181 strong rules were mined from 40 target websites and 56,096 web pages were associated with global cyberspace security. Moreover, this study analyzed support, confidence, promotion, leverage, and reliability to achieve comprehensive coverage of data. A total of 15,661 sites mentioned cyberspace security-related words from the total sample of 22,493 professional websites, accounting for 69.6%, while only 735 sites mentioned cyberspace security-related words from the total sample of 33,603 non-professional sites, accounting for 2%. Due to restrictions of language, the number of samples of target professional websites and non-target websites is limited. Meanwhile, the number of selections of strong rules is not satisfactory. Nowadays, the cores of global cyberspace security issues include internet sovereignty, cyberspace security, cyber attack, cyber crime, data leakage, and data protection.


Crucial role of TRPC6 in maintaining the stability of HIF-1α in glioma cells under hypoxia.
Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor responsible for the expression of a broad range of genes that facilitate acclimatization to hypoxia. Its stability is predominantly controlled by rapid hydroxylation of two proline residues in its α-subunit. However, how the rapid hydroxylation of HIF-1α is regulated is not fully understood. Here, we report that transient receptor potential canonical (TRPC) 6 channels control hydroxylation and stability of HIF-1α in human glioma cells under hypoxia. TRPC6 was rapidly activated by IGF-1R-PLCγ-IP3R pathway upon hypoxia. Inhibition of TRPC6 enhanced the levels of α-ketoglutarate and promoted hydroxylation of HIF-1α to suppress HIF-1α accumulation without affecting its transcription or translation. Dimethyloxalylglycine N-(methoxyoxoacetyl)-glycine methyl ester (DMOG), an analog of α-ketoglutarate, reversed the inhibition of HIF-1α accumulation. Moreover, TRPC6 regulated GLUT1 (also known as SLC2A1) expression in a manner that was dependent on HIF-1α accumulation to affect glucose uptake during hypoxia. Our results suggest that TRPC6 regulates metabolism to affect HIF-1α stability and consequent glucose metabolism in human glioma cells under hypoxia.


Diabetic Striatopathy: A New Challenge in Type 1 Pediatric Diabetic Patients.
Diabetic striatopathy is a neurological condition in patients with diabetes characterized by hemichorea-hemiballismus due to vascular and metabolic derangements in basal ganglia. This is a known entity in type 2 diabetic adult patients; however, seen rarely in pediatric patients with type 1 diabetes. Diabetic striatopathy develops in patients with poor glycemic control in the absence of ketosis. The patient tolerates hyperglycemia for a long time, which results in metabolic injury.