Effect of saffron (Crocus sativus L.) and endurance training on mitochondrial biogenesis, endurance capacity, inflammation, antioxidant, and metabolic biomarkers in Wistar rats.
We aimed to evaluate the effect of saffron (Crocus Sativus L.) treatment on endurance capacity, mitochondrial biogenesis, inflammation, antioxidant, and metabolic biomarkers in Wistar rats. Forty male rats were allocated equally into four groups: Saffron, Exercise and Saffron, Exercise and Placebo, and Placebo. Endurance training was accomplished on a specified rodent motor-driven treadmill. Running to fatigue test and also metabolic and molecular indices were measured after eight weeks of intervention. mtDNA copy number and NRF-1 gene expression increased significantly in the Ex + S group compared to the exercised and control group (p < 0.05). Endurance capacity time increased in the Ex + S group compared to the Ex group (p < 0.05). Malondialdehyde, CPK, AST, and IL-6 decreased and antioxidant parameters including Glutathione peroxidase and Glutathione increased in the Ex + S group compared to exercised rats (p < 0.01). Saffron enhanced mitochondrial biogenesis, decreased oxidative stress, inflammation, and modulated metabolic biomarkers in exercised rats. PRACTICAL APPLICATIONS: The influence of potential nutrient factors on exercise performance has reached much attention in recent years. Athletes require an appropriate sport supplement to reimburse their fatigue and improve their resilience. Saffron (Crocus Sativus L.) is a well-known spice in the food trade which is quite popular around the world by giving a desirable taste to food. In an experimental study, we showed that saffron extract treatment during endurance training could improve endurance capacity by modulating several metabolic and genomic factors. Therefore, by relying on the results of this study and the positive effects of saffron published in previous studies, saffron could be added to sport beverages and supplements to enhance an athlete's performance.


Mouse model of subarachnoid hemorrhage: technical note on the filament perforation model.
Experiments using genetically engineered mice are regarded as indispensable to gaining a better understanding of the molecular pathophysiology in neuronal injury after subarachnoid hemorrhage (SAH). Therefore, mouse SAH models are becoming increasingly important. The circle of Willis perforation (cWp) model is the most frequently used mouse SAH model. We report and discuss the technical surgical approach, results, and difficulties associated with the cWp model, with reference to the existing literature. Our results largely confirmed previously published results. This model may be the first choice at present, because important pathologies can be reproduced in this model and most findings in the literature are based on it.


Clinical and functional outcomes of cad/cam mandibular reconstruction with free fibular flap comparing traditional versus micro-invasive intraoral surgical approaches.
The surgical incision plays a pivotal role in any surgical procedure. A good surgical approach should allow optimal visualization, respect the anatomy and ensure the best aesthetic outcome possible, especially when the lesions involve the face. In this retrospective study, carried out from June 2014 to April 2018, different types of surgical approaches to perform mandibular reconstruction were compared. Twentyone patients who underwent mandibular reconstruction with free fibular flap (FFFs) using CAD-CAM technology and Virtual Surgical Planning (VSP) were included in the study, regardless the condition, the timing of reconstruction (primary vs secondary), the number of fibular segments or the type and size of the mandibular defect. The patients were treated for mandibular defects secondary to benign or low-grade oncological lesions and different non-oncological conditions. However, patients requiring neck dissection were excluded from the study. Patients were divided into two groups according to the type of surgical approach used: 7 patients received a traditional transcervical approach together with an intraoral approach, while 14 patients were operated through an intraoral approach combined with different microinvasive approaches, including the sub-mandibular, the retro-mandibular and the preauricular approaches. Different factors were statistically compared: characteristics of the harvested fibula, surgical timing, days of hospitalization, as well as complication, functional and aesthetic outcomes. According to this study, no statistically significant differences were observed between the two groups in any of the features considered. These results support the hypothesis that the combination of different microinvasive approaches and the traditional approach are superimposable, and they can be safely exchanged when the underlying defects allow it.


Characterization of airborne particles from cleaning sprays and their corresponding respiratory deposition fractions.
Cleaning workers are exposed to many risk factors, including handling of cleaning products. Epidemiological studies show that they have a high incidence of asthma and other respiratory symptoms. Some studies have indicated an even higher incidence of asthma in individuals using cleaning sprays regularly. It is known that sprays produce an aerosol that can expose the respiratory system to chemicals. Knowledge of the physical characteristics of the airborne particles, as well as the characteristics of the gas phase, is needed to determine how they affect the respiratory tract and why they cause airway symptoms. The aim of this study was to characterize the aerosols from seven different ready-to-use trigger cleaning sprays in terms of total airborne mass fraction, particle size distribution, and new particle formation from ozone reactions. An additional aim was to calculate the respiratory deposition fraction of the measured particles. The total airborne mass fraction was determined by comparing the mass deposited on the chamber wall with the mass emitted from the bottle during spraying. Particle number concentration and size distribution of the airborne particles were measured using an aerodynamic particle sizer and a fast aerosol mobility size spectrometer. The total airborne mass fraction was between 2.7% and 32.2% of the mass emitted from the bottle, depending on the product. Between 0.0001% and 0.01% of the total airborne mass fraction consisted of residual particles. However, these particles had a mass median aerodynamic diameter between 1.9 µm and 3.7 µm, constituting a total respiratory deposition of up to 77%. New particle formation in the presence of ozone was also shown to vary between 5,000 cm-3 and 35,000 cm-3 depending on the product, in the studied settings. These findings confirm that a substantial part (up to 1/3) of the mass sprayed from the bottle does not reach the intended surface. Thus, the use of cleaning sprays can result in chemical airway exposure, with particles in the relevant size range for both nasal and alveolar deposition.


Acute respiratory tract infection visits of veterans with spinal cord injuries and disorders: rates, trends, and risk factors.
Respiratory complications are a major cause of illness and death in persons with spinal cord injuries and dysfunction (SCI&Ds). The objectives of this study were to examine rates of outpatient visits over 5 years for acute respiratory tract infections (ARIs), including pneumonia and influenza (P&I), lower respiratory tract infections (LRIs), and upper respiratory tract infections (URIs), in veterans with SCI&Ds and to determine whether individual characteristics were associated with the number of annual visits for each type of ARI. This was a longitudinal (fiscal years 1998-2002) study of ARI visits at the Veterans Health Administration (VA) in 18,693 veterans with SCI&Ds. To examine the associations between time, patient characteristics, and annual number of ARI visits, we used random effect negative binomial models. Veterans with SCI&Ds had a total of 11,113 ARI visits over the 5-year period. There was a slightly decreasing trend for LRI visits over time (P < 0.01) but no significant change for other ARIs over time. There were 30 to 35 pneumonia visits and 21 to 30 acute bronchitis visits per 1,000 SCI&D veterans per year. Older veterans were more likely than younger to have P&I visits and less likely to have URI visits (P < 0.01). Veterans with paraplegia had fewer P&I visits than subjects with tetraplegia (IRR = 0.58; Cl = 0.51-0.67). Visit rates for ARIs are stable for veterans with SCI&Ds. Identifying risk factors associated with ARI visits is an important first step to improve prevention and treatment of ARIs and to improve the health of veterans with SCI&Ds.


XPS investigation of a CdS-based photoresistor under working conditions: operando-XPS.
A noncontact chemical and electrical measurement X-ray photoelectron spectroscopy (XPS) technique is performed to investigate a CdS-based photoresistor during its operation. The main objective of the technique is to trace chemical- and location-specified surface potential variations as shifts of the XPS Cd 3d(5/2) peak position without and under photoillumination with four different lasers. The system is also modeled to extract electrical information. By analyzing the measured potential variations with this model, location-dependent resistance values are represented (i) two dimensionally for line scans and (ii) three dimensionally for areal measurements. In both cases, one of the dimensions is the binding energy. The main advantage of the technique is its ability to assess an element-specific surface electrical potential of a device under operation based on the energy deviation of core level peaks in surface domains. Detection of the variations in electrical potentials and especially their responses to the energy of the illuminating source in operando, is also shown to be capable of detecting, locating, and identifying the chemical nature of structural and other types of defects.


Trachomatous scarring among children in a formerly hyper-endemic district of Tanzania.
Associations between repeated ocular infections with Chlamydia trachomatis in childhood and conjunctival scarring in adulthood are well established. Trachomatous scarring (TS) in children has also been observed in hyper-endemic areas, but data are scant regarding childhood scarring in areas where trachoma has been reduced to hypo-endemic levels. In this cross-sectional study, a random sample of children, ages 1-9 years, were selected from 38 communities in the formerly hyper-endemic district of Kongwa, Tanzania. Each participant received an ocular examination and eye-swab test for C. trachomatis infection. Conjunctival photographs were taken and analyzed at 5x magnification to determine scarring presence and severity. Community-level case clustering was assessed using intra-class correlation coefficients, and associations between TS presence and demographic/clinical factors were assessed using contingency table analyses. 1,496 children (78% of eligible) participated in this study. The mean age was 5.5 years and 51% were female. Scarring prevalence was 2.1% (95% CI: 1.5%- 3.0%). The prevalence of follicular trachoma and ocular C. trachomatis infection were 3.2% and 6.5%, respectively. Most TS cases (68.7%) fell into the mildest category, grade S1. 18.7% were grade S2; 12.6% were grade S3. No significant associations were seen between TS presence and age, sex, follicular trachoma, or active ocular C. trachomatis infection (p-values: 0.14, 0.48, 0.27, 0.15, respectively). Thirty communities (78.9%) had 0-1 TS cases, and the most seen in any single community was four cases. Three years ago, follicular trachoma prevalence averaged 4.9% in communities with 0-1 TS cases, but 7.6% in communities with 2-4 TS cases (p-value: 0.08). In this formerly hyper-endemic district of Tanzania, TS was rare in 1-9 year-olds and usually mild when present. Communities with higher rates of follicular trachoma in the past were more likely to have ≥2 cases of scarring, but the association was not statistically significant.


The effect of modified Broström-Gould repair for lateral ankle instability on in vivo tibiotalar kinematics.
Lateral ankle instability leads to an increased risk of tibiotalar joint osteoarthritis. Previous studies have found abnormal tibiotalar joint motions with lateral ankle instability that may contribute to this increased incidence of osteoarthritis, including increased anterior translation and internal rotation of the talus under weightbearing loading. Surgical repairs for lateral ankle instability have shown good clinical results, but the effects of repair on in vivo ankle motion are not well understood. The modified Broström-Gould lateral ligament reconstruction decreases anterior translation and internal rotation of the talus under in vivo weightbearing loading conditions. Controlled laboratory study. Seven patients underwent modified Broström-Gould repair for unilateral lateral ankle instability. Ankle joint kinematics as a function of increasing body weight was studied with magnetic resonance imaging and biplanar fluoroscopy. Tibiotalar kinematics was measured in unstable ankles preoperatively and postoperatively at a mean follow-up of 12 months as well as in the uninjured contralateral ankles of the same patients. Surgical repair resulted in statistically significant decreases (expressed as mean ± standard error of the mean) in anterior translation of the talus (0.9 ± 0.3 mm; P = .018) at 100% body weight and internal rotation of the talus at 75% (2.6° ± 0.8°; P = .019) and 100% (2.7° ± 0.8°; P = .013) body weight compared with ankle kinematics measured before repair. No statistically significant differences were detected between repaired ankles and contralateral normal ankles. The modified Broström-Gould repair improved the abnormal joint motion observed in patients with lateral ankle instability, decreasing anterior translation and internal rotation of the talus. Altered kinematics may contribute to the tibiotalar joint degeneration that occurs with chronic lateral ankle instability. The findings of the current study support the efficacy of this repair in improving the abnormal ankle motion observed in these patients.


Design, Synthesis, and Biological Evaluation of Novel Fluorescent Probes Targeting the 18-kDa Translocator Protein.
A series of fluorescent probes from the 6-chloro-2-phenylimidazo[1,2-a]pyridine-3-yl acetamides ligands featuring the 7-nitro-2-oxa-1,3-diazol-4-yl (NBD) moiety has been synthesized and biologically evaluated for their fluorescence properties and for their binding affinity to the 18-kDa translocator protein (TSPO). Spectroscopic studies including UV/Vis absorption and fluorescence measurements showed that the synthesized fluorescent probes exhibit favorable spectroscopic properties, especially in nonpolar environments. In vitro fluorescence staining in brain sections from lipopolysaccharide (LPS)-injected mice revealed partial colocalization of the probes with the TSPO. The TSPO binding affinity of the probes was measured on crude mitochondrial fractions separated from rat brain homogenates in a [11 C]PK11195 radioligand binding assay. All the new fluorescent probes demonstrated moderate to high binding affinity to the TSPO, with affinity (Ki ) values ranging from 0.58 nM to 3.28 μM. Taking these data together, we propose that the new fluorescent probes could be used to visualize the TSPO.


[Study on pharmacokinetics of cefuroxime by dynamics of its distribution in oral fluid of patients with sinusitis].
A method for quantitative determination of cefuroxime in mixed saliva of patients with sinusitis by using spectrophotometer Shimadzu UV-1800, combined with the IBM PC is described. The conditions of the determination were the following: λ = 266 nm, a quartz cuvette, the analysis time of 10 minutes. The method for determination of cefuroxime is characterized by high specificity, accuracy, use of small amounts of oral fluid and expressivity. The method may be recommended for the use in the clinical practice for optimizing cefuroxime therapy in patients. The pharmacokinetics of cefuroxime was investigated by the dynamics of its distribution in the oral fluid of patients with various infectious-somatic disorders.


Effects of almitrine on genioglossal and diaphragmatic electromyograms.
We previously demonstrated dose-dependent increases in both hypoglossal and phrenic electroneurograms after almitrine in anesthetized, paralyzed, and vagotomized cats. We have now investigated the effect of this peripheral chemoreceptor stimulant on diaphragmatic and genioglossal (GG, an upper airway-maintaining muscle) electromyograms in five unanesthetized, chronically instrumented, spontaneously breathing adult cats during slow-wave sleep. In 12 studies almitrine doses of 1.0-6.0 mg/kg increased inspired minute ventilation (VI), frequency (f), and tidal volume (VT) and decreased expiratory time (TE). However, almitrine doses as high as 6.0 mg/kg failed to augment phasic inspiratory GG activity. To determine why almitrine induced phasic inspiratory upper airway activity in anesthetized, vagotomized cats but not in sleeping cats, additional studies were performed. In four dose-response studies in three pentobarbital-anesthetized cats, almitrine, 1.0-6.0 mg/kg, did not produce phasic inspiratory GG activity. Almitrine did induce phasic inspiratory GG activity in two of three studies in three vagotomized, tracheostomized, alpha-chloralose-urethan-anesthetized cats. These results suggest that almitrine would not be useful in obstructive sleep apnea, yet because almitrine markedly increased VI, f, and VT and decreased TE in unanesthetized sleeping cats the drug may be effective in patients who lack normal central neural respiratory drive, such as the preterm infant.


Accuracy of cardiac output measurements with pulse contour analysis (PulseCO) and Doppler echocardiography during off-pump coronary artery bypass grafting.
During off-pump coronary bypass grafting, surgical manipulation and dislocation of the heart may cause cardiovascular instability. Monitoring of cardiac output facilitates intraoperative haemodynamic management but pulmonary artery catheters are often considered too invasive. Pulse contour analysis and transoesophageal echocardiography could serve as alternatives, but there is controversy about their accuracies. We validated pulse contour analysis using a standard radial arterial catheter (PulseCO) and aortic Doppler flowmetry with transoesophageal echocardiography in patients undergoing off-pump coronary bypass surgery. Pulmonary arterial thermodilution served as the reference technique. In 20 patients undergoing off-pump coronary bypass, cardiac output was measured with bolus thermodilution (COTD), pulse contour analysis (COPC), and transoesophageal echocardiography (COecho) at fixed time intervals during the procedure. Data were compared using linear regression and Bland-Altman analysis. At the end of the procedure, dobutamine was infused at a rate of 2.5 microg kg(-1) min(-1) in six patients to study the agreement between methods in quantifying changes in cardiac output. Comparison between COPC and COTD showed a bias +/- limits of agreement of -0.03 +/- 1.30 L min(-1) (mean error 29%). Doppler echocardiography was not always feasible when the heart was displaced from the oesophagus and had lower accuracy: bias +/- limits of agreement vs. COTD was 0.45 +/- 1.93 (mean error 43%). Increases in cardiac output induced by dobutamine were well quantified both by pulse contour analysis (COPC = 0.76 x COTD + 0.58; r(2) = 0.65) and Doppler, although the latter tended to overestimate these changes (COecho = 1.58 x COTD - 0.13; r(2) = 0.53). Calibrated pulse contour analysis using the PulseCO system is an acceptable technique to measure cardiac output non-invasively in off-pump coronary bypass patients. Doppler echocardiography performs less well and is not always feasible with transoesophageal echocardiography when the heart is displaced.


Penetration of cefprozil into middle ear fluid of patients with otitis media.
Penetration of cefprozil into the middle ear fluid was investigated in patients with chronic otitis media. A total of 89 patients ranging from 7 months to 11 years old participated in the study. The middle ear fluid was removed by ventilation tubes inserted through the tympanic membrane at times ranging from 0.38 to 5.97 h after oral administration of a single dose of 15 or 20 mg/kg of body weight. A blood sample was also collected as soon as the middle ear fluid was removed. Plasma samples were analyzed for the concentration of cefprozil by a high-performance liquid chromatographic assay. Middle ear fluid samples were analyzed for the concentration of cefprozil by a microbiological assay. The concentrations of cefprozil in plasma ranged from 0.38 to 15.97 micrograms/ml at the 15-mg/kg dose level and from 1.28 to 21.47 micrograms/ml at the 20-mg/kg dose level. The corresponding middle ear fluid concentrations of cefprozil ranged from 0.06 to 4.44 micrograms/ml and from 0.17 to 8.67 micrograms/ml, respectively. Cefprozil penetrates well into middle ear fluid in patients with chronic otitis media.


Serotonin immunoreactivity in auditory brainstem neurons of the postnatal monoamine oxidase-A knockout mouse.
Altered levels of extracellular serotonin (5-HT) during development cause structural abnormalities in the neural projections of sensory systems. To better understand the potential role of 5-HT in the development of auditory system projections, we examined 5-HT immunoreactivity (IR) in auditory brainstem nuclei of postnatal mice. We previously observed 5-HT-IR in the lateral superior olive (LSO) of wild type mice. In the current study, we used a genetic model (monoamine oxidase-A knockout mouse) in which brain 5-HT levels are abnormally high to improve detection of 5-HT. In the cochlear nucleus of this knockout, 5-HT-IR cell bodies were observed in the dorsal cochlear nucleus (DCN), a primary relay to the inferior colliculus (IC). In the superior olivary complex, 5-HT-IR somata were observed in the LSO, another relay to the IC. Labeled somata were also observed within the IC itself. The 5-HT immunostaining in all 3 regions was transient and was not observed beyond postnatal day 8. These results suggest that 5-HT may play a role in the branching and refinement of DCN and LSO axon collaterals within the IC, as well as IC axon collaterals within the medial geniculate body. The pattern of expression indicates that 5-HT has a developmental role in select populations of neurons of the ascending auditory pathway prior to any influences of sound-evoked activity.


Risk of hematologic malignancies after breast ductal carcinoma in situ treatment with ionizing radiation.
The increased incidence of secondary hematologic malignancies (SHM) is a well-known, potentially fatal, complication after cancer treatment. It is unknown if patients with ductal carcinoma in situ (DCIS) of the breast treated with external beam radiotherapy (RT) and who survive long-term have increased risks of secondary hematologic malignancies (SHM), especially for low/intermediate-risk subsets with limited benefits from RT. DCIS patients in Surveillance, Epidemiology, and End Results (SEER) registries (1975-2016) were identified. Relative risks (RR), hazard ratio (HR), and standardized incidence ratios (SIR) were calculated to assess the SHM risk and subsequent survival times. SHM development, defined as a nonsynchronous SHM occurring ≥1 year after DCIS diagnosis, was our primary endpoint. Of 184,363 eligible patients with DCIS, 77,927 (42.3%) in the RT group, and 106,436 (57.7%) in the non-RT group, 1289 developed SHMs a median of 6.4 years (interquartile range, 3.5 to 10.3 years) after their DCIS diagnosis. Compared with DCIS patients in the non-RT group, RT was associated with increased early risk of developing acute lymphoblastic leukemia (ALL; hazard ratio, 3.15; 95% CI, 1.21 to 8.17; P = 0.02), and a delayed risk of non-Hodgkin lymphoma (NHL; hazard ratio, 1.33; 95% CI, 1.09 to 1.62; P < 0.001). This increased risk of ALL and NHL after RT was also observed in subgroup analyses restricted to low/intermediate-risk DCIS. In summary, our data suggest that RT after breast conserving surgery for DCIS patients should be cautiously tailored, especially for low and intermediate-risk patients. Long-term SHM surveillance after DCIS diagnosis is warranted.


Selection for virulent dengue viruses occurs in humans and mosquitoes.
Dengue is the most common mosquito-borne viral disease in humans. The spread of both mosquito vectors and viruses has led to the resurgence of epidemic dengue fever (a self-limited flu-like syndrome) and the emergence of dengue hemorrhagic fever (severe dengue with bleeding abnormalities) in urban centers of the tropics. There are no animal or laboratory models of dengue disease; indirect evidence suggests that dengue viruses differ in virulence, including their pathogenicities for humans and epidemic potential. We developed two assay systems (using human dendritic cells and Aedes aegypti mosquitoes) for measuring differences in virus replication that correlate with the potential to cause hemorrhagic dengue and increased virus transmission. Infection and growth experiments showed that dengue serotype 2 viruses causing dengue hemorrhagic fever epidemics (Southeast Asian genotype) can outcompete viruses that cause dengue fever only (American genotype). This fact implies that Southeast Asian genotype viruses will continue to displace other viruses, causing more hemorrhagic dengue epidemics.


Elucidating Raman Image-Guided Differential Recognition of Clinically Confirmed Grades of Cervical Exfoliated Cells by Dual Biomarker-Appended SERS-Tag.
Ultrasensitive detection of cancer biomarkers via single-cell analysis through Raman imaging is an impending approach that modulates the possibility of early diagnosis. Cervical cancer is one such type that can be monitored for a sufficiently long period toward invasive cancer phenotype. Herein, we report a surface-enhanced Raman scattering (SERS) nanotag (SERS-tag) for the simultaneous detection of p16/K-i67, a dual biomarker persisting in the progression of squamous cell carcinoma of human cervix. A nanoflower-shaped SERS-tag, constituted of hybrid gold nanostar with silver tips to achieve maximum fingerprint enhancement from the incorporated reporter molecule, was further functionalized with the cocktail monoclonal antibodies against p16/K-i67. The recognition by the SERS-tag was first validated in cervical squamous cell carcinoma cell line SiHa as a foot-step study and subsequently implemented to different grades of clinically confirmed exfoliated cells including normal cell (NC), high-grade intra-epithelial lesion (HC), and squamous cell carcinoma (CC) samples of the cervix. Precise Raman mapped images were constituted based on the average intensity gradient of the signature Raman peaks arising from different grades of exfoliated cells. We observed a distinct intensity hike of around 10-fold in the single dysplastic HC and CC samples in comparison to NC specimen, which clearly justify the prevalence of p16/Ki-67. The synthesized probe is able to map the abnormal cells within 20 min with high reproducibility and stability for 1 mm × 1 mm mapping area with good contrast. Amidst the challenges in Raman image-guided modality, the technique was further complemented with the gold standard immunocytochemistry (ICC) dual staining analysis. Even though both are time-consuming techniques, tedious steps can be avoided and real-time readout can be achieved using the SERS mapping unlike immunocytochemistry technique. Therefore, the newly developed Raman image-guided SERS imaging emphasizes the approach of uplifting of SERS in practical utility with further improvement for clinical applications for cervical cancer detection in future.


Regulation of NAD(P)H dehydrogenase-dependent cyclic electron transport around PSI by NaHSO₃ at low concentrations in tobacco chloroplasts.
Although bisulfite at low concentrations (L-NaHSO₃) has been found to increase the cyclic electron transport around PSI (CET), its regulative mechanism remains unknown. In this work, the role of L-NaHSO₃ (0.1-500 μM) in NAD(P)H dehydrogenase-dependent CET (the NDH pathway) was investigated. After treatment of tobacco leaves with L-NaHSO₃, the NDH pathway, as reflected by a transient post-illumination increase in Chl fluorescence, the dark reduction of P700+ after far-red light and the amount of NDH, was increased after the light-dark-light transition, but was slightly lowered under continuous light. Meanwhile, the linear electron transport (LET) was accelerated by L-NaHSO₃ under both the light regimes. Experiments in thylakoids further demonstrated that both LET, monitored by light-dependent oxygen uptake, and CET, as determined from the NADPH-dependent oxygen uptake and dark reduction of P700+, were enhanced by L-NaHSO₃ and the enhancements were abolished by superoxide dismutase. Furthermore, L-NaHSO₃-induced CET was partially impaired in thylakoids of the ΔndhCKJ mutant, while L-NaHSO₃-induced LET was not affected. Based on these results, we propose that the photooxidation of L-NaHSO₃ initiated by superoxide anions in PSI regulates NDH pathway to maintain efficient photosynthesis.


Expectant management of pregnancies complicated by fetal growth restriction without any evidence of placental dysfunction at term: Comparison with routine labor induction.
To assess the feasibility and practicality of expectant management for pregnancies with fetal growth restriction (FGR) at term without evidence of placental dysfunction. We reviewed the records of pregnancies with an estimated fetal weight ≤ 1.5 SD below the mean at 37 weeks of gestation. We excluded elective cesarean deliveries and pregnancies that, at 37 weeks, were complicated by oligohydramnios, decreased fetal cerebroplacental ratio, or pregnancy-related hypertensive disorders. Prior to May 2013, we performed routine labor induction for FGR at term; after that time, we used routine expectant management. The rate of delivery by cesarean or instrumental assist and the rate of neonatal morbidity were compared between the groups. The gestational age at delivery and the neonatal birthweight were higher in the expectant management policy group (39+4 vs 38+1 weeks; 2405 vs 2205 g). The cesarean rate (7/77 vs 7/73) and the instrumental delivery rate (5/77 vs 6/73) did not differ. Neonatal hypoglycemia and hyperbilirubinemia were significantly less frequent (10/77 vs 21/73; 7/77 vs 20/73) in the expectant management policy group. Seven patients in the expectant management policy group underwent emergency cesarean delivery; five of these (71%) had required labor induction because of progression to oligohydramnios. Expectant management policy for FGR at term can reduce neonatal morbidity without increasing maternal risk or the cesarean rate. Caution should be used, however, during labor if oligohydramnios develops during expectant management.


The effect of a low-dose oral contraceptive on serum testosterone levels in polycystic ovary disease.
A study was designed to determine the effect of a low-estrogen-dosage oral contraceptive on the serum concentration of testosterone-binding globulin (TBG) and total and unbound testosterone in patients with polycystic ovary disease (PCOD). Treatment with norethindrone 0.5 mg and ethinyl estradiol 0.035 mg (Modicon, Ortho) increased the TBG concentration and reduced the unbound serum testosterone concentration.


Cyclin E associates with components of the pre-mRNA splicing machinery in mammalian cells.
Cyclin E-cdk2 is a critical regulator of cell cycle progression from G1 into S phase in mammalian cells. Despite this important function little is known about the downstream targets of this cyclin-kinase complex. Here we have identified components of the pre-mRNA processing machinery as potential targets of cyclin E-cdk2. Cyclin E-specific antibodies coprecipitated a number of cyclin E-associated proteins from cell lysates, among which are the spliceosome-associated proteins, SAP 114, SAP 145, and SAP 155, as well as the snRNP core proteins B' and B. The three SAPs are all subunits of the essential splicing factor SF3, a component of U2 snRNP. Cyclin E antibodies also specifically immunoprecipitated U2 snRNA and the spliceosome from splicing extracts. We demonstrate that SAP 155 serves as a substrate for cyclin E-cdk2 in vitro and that its phosphorylation in the cyclin E complex can be inhibited by the cdk-specific inhibitor p21. SAP 155 contains numerous cdk consensus phosphorylation sites in its N terminus and is phosphorylated prior to catalytic step II of the splicing pathway, suggesting a potential role for cdk regulation. These findings provide evidence that pre-mRNA splicing may be linked to the cell cycle machinery in mammalian cells.


Brightness versus apparent contrast. 3: Blurred disks and concentric cosine gratings.
Matching either the centre-brightness or the apparent contrast of incremental 1-deg disks, with varying edge-sharpness, yields quite different results. These suggest that the maximum brightness gradient at the edge determines apparent-contrast perception. However, no significant differences are found in matching the brightness maxima, the brightness minima, or the apparent contrast of concentric cosine gratings with varying spatial frequency. This means that spatial frequency influences both brightness extremes in the same way, and that apparent contrast is a function of the difference between the brightness extremes. The grating results therefore deviate from the results obtained with sharp as well as blurred disks. These contradictions complicate the construction of a model which unifies suprathreshold disk and grating perception.


Specificity of OKT4+ cytotoxic T lymphocyte clones.
OKT4+, HLA-DR-specific CTL were cloned by limiting dilution, and two clones were evaluated. One clone, B8, specifically recognized DR6 antigens, whereas another cloned, C6, recognized an Ia-like determinant on some DR 3, 5, and 6 target cells. Both clones were OKT3+, OKT4+, and OKT8-, and their cytolysis could be blocked by OKT3 and OKT4, but not OKT8, antibodies. A panel of monoclonal antibodies that recognize DR molecules blocked target cell recognition by these OKT+ CTL. Although cloned B8 recognized a DR6-specific determinant, clone C6 appeared to recognize a supratypic determinant that may be common to some DR molecules (e.g., MT2) or possibly another human Ia-like antigen (e.g., SB). The availability of OKT+ CTL clones should help to dissect the Ia-like antigens recognized by human T cells.


Measurements of methane emissions at natural gas production sites in the United States.
Engineering estimates of methane emissions from natural gas production have led to varied projections of national emissions. This work reports direct measurements of methane emissions at 190 onshore natural gas sites in the United States (150 production sites, 27 well completion flowbacks, 9 well unloadings, and 4 workovers). For well completion flowbacks, which clear fractured wells of liquid to allow gas production, methane emissions ranged from 0.01 Mg to 17 Mg (mean = 1.7 Mg; 95% confidence bounds of 0.67-3.3 Mg), compared with an average of 81 Mg per event in the 2011 EPA national emission inventory from April 2013. Emission factors for pneumatic pumps and controllers as well as equipment leaks were both comparable to and higher than estimates in the national inventory. Overall, if emission factors from this work for completion flowbacks, equipment leaks, and pneumatic pumps and controllers are assumed to be representative of national populations and are used to estimate national emissions, total annual emissions from these source categories are calculated to be 957 Gg of methane (with sampling and measurement uncertainties estimated at ± 200 Gg). The estimate for comparable source categories in the EPA national inventory is ~1,200 Gg. Additional measurements of unloadings and workovers are needed to produce national emission estimates for these source categories. The 957 Gg in emissions for completion flowbacks, pneumatics, and equipment leaks, coupled with EPA national inventory estimates for other categories, leads to an estimated 2,300 Gg of methane emissions from natural gas production (0.42% of gross gas production).


Differentiation of nerve terminals in the crayfish opener muscle and its functional significance.
Junctional potentials (jp's) recorded from superficial distal fibers of the crayfish opener muscle are up to 50 times larger than jp' in superficial central fibers when the single motor axon that innervates the muscle is stimulated at a frequency of 1/sec or less. At 80/sec, in contrast, central jp's are up to four times larger than those observed in distal fibers. The tension produced by single muscle fibers of either type is directly proportional to the integral of the time-voltage curve minus an excitation-contraction coupling threshold of 3 mv. Distal fibers therefore produce almost all the total muscle tension at low frequencies of stimulation and central fibers add an increasingly greater contribution as their nerve endings begin to facilitate in response to increased rate of motor discharge. Differentiation of muscle membrane characteristics (input resistance, space constant, time constant) cannot account for these differences in facilitation ratios. The mechanism of neuronal differentiation is not based upon the size or effectiveness of transmitter quanta, since equal sized jp's have equal variances;: mjp sizes and variances are also equal. No differences were found between fiber types in rates of transmitter mobilization, density of innervation, or the relationship between transmitter release and terminal depolarization. Single terminals on distal fibers were found to release transmitter with a greater probability than central terminals. More effective invasion of distal terminals by the nerve impulse at low frequencies can account for the difference.


Position-dependent image characteristics of a CCD-based full-field digital mammography system.
Full-field digital mammography imaging systems have been investigated extensively. However, most investigations focus on the quality assessment of the entire image. In this article, we present the results of experimental measurements on the position-dependent image characteristics of a CCD array-based digital imaging system. Objective image quality parameters such as noise power spectrum (NPS) and signal-to-noise ratio (SNR), which are also frequency-dependent, are employed for this investigation. The image detector uses 12 CCDs arranged in a 4 × 3 array to cover a field of 18 cm × 24 cm with a single x-ray exposure. Totally 18 sub-areas were chosen as the regions-of-interest (ROIs) for each full-field image to study position-dependent characteristics. Our experimental results indicate that the image quality at different positions of the full-field image exhibit slightly variance due to the characteristic diversity of the CCDs and due to the oblique angle of the ROIs to the x-ray source. The image seams caused by the physical gaps between adjacent CCDs do not increase the noise components significantly to the composite full-field image. The x-ray energy-dependence of NPS and SNR was also studied.


Fluorouracil cardiotoxicity.
To review the clinical manifestations, postulated mechanisms, and therapeutic implications of fluorouracil-induced cardiac toxicity. A MEDLINE search was used to identify pertinent literature. Studies and case reports on fluorouracil cardiotoxicity were identified through a MEDLINE search. A manual review of bibliographies of identified articles was performed to ensure that all pertinent articles were included. Data pertaining to all aspects of fluorouracil cardiac toxicity, including pathogenesis, predisposing factors, clinical manifestations, and therapeutic implications, were evaluated. Estimates from large series suggest a 1.6-2.3 percent incidence of clinically demonstrated cardiotoxicity. Predisposing factors include the presence of coronary artery disease and concurrent radiotherapy. Postulated mechanisms include direct myocardial ischemia, coronary spasm, or cardiotoxic impurities in fluorouracil formulation. Clinical manifestations include chest pain, nausea, diaphoresis with typical ischemic electrocardiographic (ECG) changes, relieved to normal after stopping the drug therapy. Nitrates and calcium-channel blockers do not protect against cardiotoxicity. Fluorouracil cardiotoxicity may be much more common and clinically significant than previously thought. A high index of suspicion for cardiotoxicity must be maintained when the drug is administered, especially in the presence of heart disease and concomitant radiation therapy. In the presence of chest pain, it is mandatory to stop the infusion and, if possible, to replace fluorouracil with another chemotherapeutic agent.


Duodenal Crohn's disease complicated by common bile duct obstruction: report of a case and review of the literature.
A 28-year-old woman with Crohn's disease involving the duodenum and terminal ileum presented with biochemical evidence of incomplete, extrahepatic biliary obstruction. Percutaneous transhepatic cholangiography showed partial obstruction of the intramural duodenal portion of the common bile duct. Cholangiography was complicated by cholangitis. Surgical decompression of the biliary system and bypass of the affected duodenal segment were performed after intraoperative confirmation of Crohn's disease involving the ileum, duodenum, and ampulla of Vater. The patient made a complete recovery and all previously abnormal cholestatic liver function test results returned to normal.


Using the prone position for ventilated patients with respiratory failure: a review.
this review explored the evidence relating to prone positioning in ventilated patients diagnosed with respiratory failure, including acute lung injury (ALI) or adult respiratory distress syndrome (ARDS). mortality rates for ventilated patients with ALI or ARDS are high, and there is a growing body of evidence suggesting that the position these patients are nursed in may influence clinical outcomes. However, there are no guidelines to inform nursing practice in positioning these patients. Medline, Scopus, Cinahl and the Cochrane Library databases were searched for original research reports or systematic reviews of evidence between 2000 and 2009. Reference lists of retrieved papers were hand searched and included studies were analysed using the Critical Appraisal and Skills Programme framework. A narrative data synthesis considered the strengths and limitations of studies, and findings were collated and interpreted. Application of the search strategy identified a systematic review, currently underway, which has not yet reported and 14 relevant studies eligible for inclusion in this review. Analysis showed considerable variation in study design, but suggests that PaO(2) /FiO(2) ratio, incidence of VAP and mortality may be positively affected by prone positioning. evidence of the clinical benefits associated with prone positioning is inconclusive and provides little guidance for nursing practice. There is a need for further research into the clinical outcomes of prone positioning, and greater understanding of the practicalities of prone positioning critically ill patients is required. nurses have a central role to play in the continual assessment and management of this patient group, including the position they are nursed in, not only to ensure the best clinical outcomes but also to provide care and comfort to the patient and their family. It is therefore important that their nursing practice and interventions are informed by the best available evidence.


Vascular endothelial growth factor (VEGF), VEGF receptors and their inhibitors for antiangiogenic tumor therapy.
Vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) have crucial roles in both physiological and pathological angiogenesis. The VEGF family consists of VEGF-A (generally called VEGF), VEGF-B, VEGF-C, VEGF-D, and placental growth factor (PlGF). These peptides show different affinities for VEGFR subtypes. VEGFR exists as three subtypes, VEGFR-1, VEGFR-2, and VEGFR-3, and is structurally related to platelet-derived growth factor receptors. All subtypes possess seven immunoglobulin-like domains in the extracellular region and a tyrosine kinase domain in the intracellular region. VEGF-A activates VEGFR-1 and VEGFR-2, whereas VEGF-B and PlGF bind to only VEFGR-1. VEGF-C and VEGF-D only bind to VEGFR-3. VEGFR-1 (fms-like tyrosine kinase-1, Flt-1) negatively regulates embryonic vasculogenesis and is involved in tumor angiogenesis via activation of monocytes and macrophages. VEGFR-2 (KDR in humans or Flk-1 in mice) is predominantly responsible for both embryonic vasculogenesis and tumor angiogenesis. In contrast, VEGFR-3 (Flt-4) regulates lymphangiogenesis. Consequently, VEGF-A and VEGFR-2 are currently the main targets for antiangiogenic therapy. Bevacizumab is a humanized monoclonal antibody against VEGF-A, and aflibercept (VEGF-Trap) is a soluble fusion protein of the extracelluar domain of VEGFR-1 and VEGFR-2 and the Fc region of immunoglobulin G (IgG). They neutralize VEGF-A, resulting in prevention of tumor angiogenesis. VEGFR tyrosine kinase inhibitors such as sunitinib and sorafenib are also effective in antiangiogenic tumor therapy by inhibiting VEGFR signaling. Anti-VEGF drugs are a promising therapy for cancer patients.


Site Selectivity of Peptoids as Azobenzene Scaffold for Molecular Solar Thermal Energy Storage.
Storing solar energy is a key challenge in modern science. MOlecular Solar Thermal (MOST) systems, in particular those based on azobenzene switches, have received great interest in the last decades. The energy storage properties of azobenzene (t1/2 <4 days; ΔH~270 kJ/kg) must be improved for future applications. Herein, we introduce peptoids as programmable supramolecular scaffolds to improve the energy storage properties of azobenzene-based MOST systems. We demonstrate with 3-unit peptoids bearing a single azobenzene chromophore that dynamics of the MOST systems can be tuned depending on the anchoring position of the photochromic unit on the macromolecular backbone. We measured a remarkable increase of the half-life of the metastable form up to 14 days at 20 °C for a specific anchoring site, significantly higher than the isolated azobenzene moiety, thus opening new perspectives for MOST development. We also highlight that liquid chromatography coupled to mass spectrometry does not only enable to monitor the different stereoisomers during the photoisomerization process as traditionally done, but also allows to determine the thermal back-isomerization kinetics.


Racial differences in concussion diagnosis and mechanism of injury among adults presenting to emergency departments across the United States.
The purpose of this study was to examine the association between race and concussion diagnosis as well as the association between race and mechanism of injury (MOI) for concussion diagnoses in adult patients (>19 years old) visiting the emergency department (ED). A retrospective analysis of patient visits to the ED for concussion between 2010 and 2018, using the National Hospital Ambulatory Medical Care Survey, was conducted. Outcome measures included concussion diagnosis and MOI. Multivariable and multinomial logistic regression analyses were conducted to assess associations between race and outcome variables. The results were weighted to reflect population estimates with a significance set at p < 0.05. Overall, 714 patient visits for concussions were identified, representing an estimated 4.3 million visits nationwide. Black adults had lower odds of receiving a concussion diagnosis [p < 0.05, Odds Ratio (OR), 0.54; 95% Confidence Interval (CI), 0.38-0.76] compared to White adults in the ED. There were no significant differences in MOI for a concussion diagnosis by race. Racial differences were found in the ED for concussion diagnosis. Disparities in concussion diagnosis for Black or other minoritized racial groups could have significant repercussions that may prolong recovery or lead to long-term morbidity.


Pathogenesis of cardiovascular events in BCR-ABL1-negative myeloproliferative neoplasms.
Thrombosis, both in arterial and venous territories, is the major complication of myeloproliferative neoplasms and is responsible for a high rate of morbidity and mortality. The currently accepted risk factors are an age over 60 years and a history of thrombosis. However, many complex mechanisms contribute to this increased prothrombotic risk, with involvement of all blood cell types, plasmatic factors, and endothelial cells. Besides, some cardiovascular events may originate from arterial vasospasm that could contribute to thrombotic complications. In this review, we discuss recent results obtained in mouse models in the light of data obtained from clinical studies. We emphasize on actors of thrombosis that are currently not targeted with current therapeutics but could be promising targets, i.e, neutrophil extracellular traps and vascular reactivity.


Frequency-Tagging Electroencephalography of Superimposed Social and Non-Social Visual Stimulation Streams Reveals Reduced Saliency of Faces in Autism Spectrum Disorder.
Individuals with autism spectrum disorder (ASD) have difficulties with social communication and interaction. The social motivation hypothesis states that a reduced interest in social stimuli may partly underlie these difficulties. Thus far, however, it has been challenging to quantify individual differences in social orientation and interest, and to pinpoint the neural underpinnings of it. In this study, we tested the neural sensitivity for social versus non-social information in 21 boys with ASD (8-12 years old) and 21 typically developing (TD) control boys, matched for age and IQ, while children were engaged in an orthogonal task. We recorded electroencephalography (EEG) during fast periodic visual stimulation (FPVS) of social versus non-social stimuli to obtain an objective implicit neural measure of relative social bias. Streams of variable images of faces and houses were superimposed, and each stream of stimuli was tagged with a particular presentation rate (i.e., 6 and 7.5 Hz or vice versa). This frequency-tagging method allows disentangling the respective neural responses evoked by the different streams of stimuli. Moreover, by using superimposed stimuli, we controlled for possible effects of preferential looking, spatial attention, and disengagement. Based on four trials of 60 s, we observed a significant three-way interaction. In the control group, the frequency-tagged neural responses to faces were larger than those to houses, especially in lateral occipito-temporal channels, while the responses to houses were larger over medial occipital channels. In the ASD group, however, faces and houses did not elicit significantly different neural responses in any of the regions. Given the short recording time of the frequency-tagging paradigm with multiple simultaneous inputs and the robustness of the individual responses, the method could be used as a sensitive marker of social preference in a wide range of populations, including younger and challenging populations.


Enhanced thermophysical properties via PAO superstructure.
For the last few years, molten salt nanomaterials have attracted many scientists for their enhanced specific heat by doping a minute concentration of nanoparticles (up to 1% by weight). Likewise, enhancing the specific heat of liquid media is important in many aspects of engineering such as engine oil, coolant, and lubricant. However, such enhancement in specific heat was only observed for molten salts, yet other engineering fluids such as water, ethylene glycol, and oil have shown a decrease of specific heat with doped nanoparticles. Recent studies have shown that the observed specific heat enhancement resulted from unique nanostructures that were formed by molten salt molecules when interacting with nanoparticles. Thus, such enhancement in specific heat is only possible for molten salts because other fluids may not naturally form such nanostructures. In this study, we hypothesized such nanostructures can be mimicked through in situ formation of fabricated nano-additives, which are putative nanoparticles coated with useful organic materials (e.g., polar-group-ended organic molecules) leading to superstructures, and thus can be directly used for other engineering fluids. We first applied this approach to polyalphaolefin (PAO). A differential scanning calorimeter (DSC), a rheometer, and a customized setup were employed to characterize the heat capacity, viscosity, and thermal conductivity of PAO and PAO with fabricated nano-additives. Results showed 44.5% enhanced heat capacity and 19.8 and 22.98% enhancement for thermal conductivity and viscosity, respectively, by an addition of only 2% of fabricated nanostructures in comparison with pure PAO. Moreover, a partial melting of the polar-group-ended organic molecules was observed in the first thermal cycle and the peak disappeared in the following cycles. This indicates that the in situ formation of fabricated nano-additives spontaneously occurs in the thermal cycle to form nanostructures. Figure of merit analyses have been performed for the PAO superstructure to evaluate its performance for heat storage and transfer media.


Tunable chirped microwave photonic filter employing a dispersive Mach-Zehnder structure.
A Mach-Zehnder structure with modulation in one arm and dispersive time delay in the other is proposed to implement highly flexible single-bandpass chirped microwave photonic filters based on broadband optical sources. Both the amplitude response and the time delay slope can be fully reconfigured via control of the optical spectra and dispersion. The passband can also be widely tuned without changing the shape. A chirped filter with a bandwidth of ∼4 GHz, a delay slope of ∼-0.6 ns/GHz, and a tunability up to 40 GHz is demonstrated experimentally.


Icariin Regulates the hsa_circ_0003159/eIF4A3/bcl-2 Axis to Promote Gastric Cancer Cell Apoptosis.
To clarify the mechanism of icariin (ICA) promoting gastric cancer (GC) cell apoptosis by regulating circ_0003159/eIF4A3/bcl-2 axis. The mRNA or protein levels were detected by qRT-PCR or the western blot. The interaction between eIF4A3 protein and circ_0003159 or eIF4A3 protein and bcl-2 mRNA were validated by RNA pull down assays and the RNA immunoprecipitation (RIP) assay. The cell viability was measured by the cell counting kit (CCK)-8 kit. The cell apoptosis was measured by flow cytometry. Compared with the group Vector, the ratio of cytoplasmic eIF4A3/nuclear eIF4A3 in the cell with circ_0003159 overexpression was significantly higher. RIP and RNA pull down results proved the interaction between eIF4A3 and circ_0003159. The RIP assay further validated the interaction between eIF4A3 and bcl-2. By gain or loss of the functional experiment, hsa_circ_0003159 was proved to recruit eIF4A3 to inhibit bcl-2 expression. Hsa_circ_0003159 regulates eIF4A3/bcl-2 to reduce GC cell viability and increase apoptosis Furthermore, ICA regulates hsa_circ_0003159/eIF4A3/bcl-2 axis to inhibit GC cell activity and induce GC cell apoptosis in vitro. These data showed that ICA could effectively reduce the GC cell activity and induce GC cell apoptosis via hsa_circ_0003159/eIF4A3/bcl-2 axis, which provides new theoretical evidence for the treatment of GC by ICA.


Identifying spin bias of nonsignificant findings in biomedical studies.
The purpose of this research note is to share a technique for the identification of spin bias that we developed as part of a living systematic review on the cardiovascular testing of e-cigarette substitution for cigarette smoking. While some researchers have remarked on the subjective nature of ascertaining spin bias, our technique objectively documents forms of spin bias arising from the misrepresentation of nonsignificant findings and from the omission of data. We offer a two-step process for the identification of spin bias consisting of tracking data and findings and recording of data discrepancies by describing how the spin bias was produced in the text. In this research note, we give an example of the documentation of spin bias from our systematic review. Our experience was that nonsignificant results were presented as causal or even as significant in the Discussion of studies. Spin bias distorts scientific research and misleads readers; therefore it behooves peer reviewers and journal editors to make the effort to detect and correct it.


Engineered expression of the Coxsackie B and adenovirus receptor (CAR) in human dendritic cells enhances recombinant adenovirus-mediated gene transfer.
Dendritic cells (DCs) are key antigen-presenting cells (APCs) that act as central modulators of cellular immune responses. Genetic modification of DCs has considerable therapeutic potential in the treatment of a wide spectrum of diseases, including cancer and persistent viral infection. In this report, we show that pre-treatment of DCs with a recombinant adenovirus encoding the major adenovirus receptor, Coxsackie B and adenovirus receptor (CAR), significantly increased the uptake of recombinant adenoviruses (Ads) by primary immature monocyte-derived DCs. This could be correlated with CAR mRNA and surface protein expression. Transduction of DCs by recombinant adenoviruses did not significantly alter cellular viability. Therefore, we propose that pre-treatment of DCs with Ad5-CAR is one strategy to increase the susceptibility of DCs to transduction by recombinant Ads.


Laparoscopic and robotic transperitoneal repair of retrocaval ureter: A comparison of the surgical outcomes from two centres with a comprehensive literature review.
The use of minimally invasive surgical approaches for the repair of retrocaval ureter (RCU) has been increased in time. However, the results of the robotic approach have not yet been compared with those of open or laparoscopic approaches. We aimed to compare the results of laparoscopic and robotic transperitoneal repair of RCU from two centres. Initially, we performed a systemic literature search using MEDLINE/PubMed and Google Scholar about the RCU. Finally, a comparison of the efficacy and outcomes of the laparoscopic and robotic transperitoneal approaches for RCU repair was performed with the results of two centers. The mean age was 27.5 ± 3.6 years. The mean operative time was 147 ± 63.6 min. The median estimated blood loss was 100 (20-423.9) ml. The median drain removing time and hospital stay were 2 (2-3) and 3 (2-4) days, respectively. The mean follow-up period was 17.85 ± 14.6 months. All of the parameters were similar between the laparoscopic and robotic repair groups except for the mean operative time. It was significantly shorter in robotic repair group than those of laparoscopic repair group (P = 0.02). Furthermore, a ureteral stricture of the anastomotic segment was detected in a patient treated with laparoscopy during the follow-up. Robotic transperitoneal approach may shorten the operative time enabling a greater comfort in repair of RCU.


MR image texture analysis applied to the diagnosis and tracking of Alzheimer's disease.
We assess the value of magnetic resonance (MR) image texture in Alzheimer's disease (AD) both as a diagnostic marker and as a measure of progression. T1-weighted MR scans were acquired from 40 normal controls and 24 AD patients. These were split into a training set (20 controls, 10 AD) and a test set (20 controls, 14 AD). In addition, five control subjects and five AD patients were scanned repeatedly over several years. On each scan a texture feature vector was evaluated over the brain; this consisted of 260 measures derived from the spatial gray-level dependence method. A stepwise discriminant analysis was applied to the training set, to obtain a linear discriminant function. In the test set, this function yielded significantly different values for the control and AD groups (p < 10(-4)) with only small group overlap; a classification rate of 91% was obtained. For the repeatedly scanned control subjects, the median increment in the discriminant function between successive scans of 0.12 was not significantly different from zero (p > 0.05); for the repeatedly scanned AD patients the corresponding median increment of 1.4 was significantly different from zero (p < 0.05). MR image texture may be a useful aid in the diagnosis and tracking of Alzheimer's disease.


Passive leg raising as an indicator of fluid responsiveness in patients with severe sepsis.
In the management of critically ill patients, the assessment of volume responsiveness and the decision to administer a fluid bolus constitute a common dilemma for physicians. Static indices of cardiac preload are poor predictors of volume responsiveness. Passive leg raising (PLR) mimics an endogenous volume expansion (VE) that can be used to predict fluid responsiveness. This study was to assess the changes in stroke volume index (SVI) induced by PLR as an indicator of fluid responsiveness in mechanically ventilated patients with severe sepsis. This was a prospective study. Thirty-two mechanically ventilated patients with severe sepsis were admitted for VE in ICU of the First Affiliated Hospital, Zhejiang University School of Medicine and Ningbo Medical Treatment Center Lihuili Hospital from May 2010 to December 2011. Patients with non-sinus rhythm or arrhythmia, parturients, and amputation of the lower limbs were excluded. Measurements of SVI were obtained in a semi-recumbent position (baseline) and during PLR by the technique of pulse indicator continuous cardiac output (PiCCO) system prior to VE. Measurements were repeated after VE (500 mL 6% hydroxyethyl starch infusion within 30 minutes) to classify patients as either volume responders or non-responders based on their changes in stroke volume index (ΔSVI) over 15%. Heart rate (HR), systolic artery blood pressure (ABPs), diastolic artery blood pressure (ABPd), mean arterial blood pressure (ABPm), mean central venous pressure (CVPm) and cardiac index (CI) were compared between the two groups. The changes of ABPs, ABPm, CVPm, and SVI after PLR and VE were compared with the indices at the baseline. The ROC curve was drawn to evaluate the value of ΔSVI and the change of CVPm (ΔCVPm) in predicting volume responsiveness. SPSS 17.0 software was used for statistical analysis. Among the 32 patients, 22 were responders and 10 were non-responders. After PLR among the responders, some hemodynamic variables (including ABPs, ABPd, ABPm and CVPm) were significantly elevated (101.2±17.6 vs.118.6±23.7, P=0.03; 52.8±10.7 vs. 64.8±10.7, P=0.006; 68.3±11.7 vs. 81.9±14.4, P=0.008; 6.8±3.2 vs. 11.9±4.0, P=0.001). After PLR, the area under curve (AUC) and the ROC curve of ΔSVI and ΔCVPm for predicting the responsiveness after VE were 0.882±0.061 (95%CI 0.759-1.000) and 0.805±0.079 (95%CI 0.650-0.959) when the cut-off levels of ΔSVI and ΔCVPm were 8.8% and 12.7%, the sensitivities were 72.7% and 72.7%, and the specificities were 80% and 80%. Changes in ΔSVI and ΔCVPm induced by PLR are accurate indices for predicting fluid responsiveness in mechanically ventilated patients with severe sepsis.


Prediction of striped cylindrical micelles (SCMs) formed by dodecyl-β-d-maltoside (DDM) surfactants.
Using fully atomistic and coarse-grained (CG) molecular dynamics (MD) simulations, we report, for the first time, the self-assembly of initially randomly dispersed dodecyl-β-d-maltoside (DDM) surfactants into a striped cylindrical micelle (SCM) with lamellae of surfactant heads and tails alternating along the cylindrical axis, with both heads and tails in contact with the water. By changing the interaction strength of the head group with water relative to itself, we find that such micelles are most likely for head groups with marginal solubility in the water solvent. Unlike the surfactants in a regular cylindrical micelle, whose tails are in the fluid micelle interior, the diffusion of DDM surfactants along the micelle body is blocked by the lamellar patterning. As a consequence, branches cannot slide along the micelle body and surfactant molecules cannot exchange between the micelle body and the branch, which should have a significant impact on the rheological properties of these micelles.


Continuous manipulation of doughnut focal spot in a large scale.
We theoretically demonstrate that the doughnut focal spot can continuously be manipulated by synthetically using various beam modulation techniques. Comparatively, a more evident effect can be expected by different orders of phase modulation, while accurate manipulation stems from changing the phase diversity between two arms in an image inverting interferometer (III). The size of central dark spot can thus be continuously adjusted in a theoretically infinite scale, although it may actually be limited by resolution of Spatial Light Modulator (SLM). This approach brings additional flexibility to many applications, such as optical tweezers.


Safety of anti-tumor necrosis factor therapies in arthritis patients.
Inflammatory and rheumatic arthritis remain leading causes of disability worldwide. The arthritis therapeutic area commands the largest market for the prescription of biological and non-steroidal anti-inflammatory drugs (NSAID). Yet biotechnology and pharmaceutical companies conducting research and providing therapeutics in this area frequently face challenges in patient safety. The purpose of our study was to assess safety of anti-tumor necrosis factor therapies in arthritis patients. The present study systematically reviews adverse events of biologicals alone or in the presence of NSAIDs and other immunosuppressant therapeutics such as disease-modifying antirheumatic drugs (DMARD). We assessed the rheumatology literature that included clinical trials with anti-tumor necrosis factor (TNF) biologicals and case reports published between 2010 and 2014. Currently approved anti-TNF biologicals in arthritis include the monoclonal antibodies infliximab, adalimumab, certolizumab pegol and golimumab, and the fusion protein etanercept. The most frequently-reported adverse event was infection. We grouped the adverse reactions as immune-mediated, hypersensitivity syndrome reactions including cutaneous and hepatic manifestation, neurological, hematological, and malignancy. Most adverse events are due to the failure of host immunological control, which involves susceptibility to the drug itself, or de novo infection or reactivation of a latent bacterial or viral infection, often with a different expression of disease. Drug-induced liver injury associated with anti-TNF biologicals must be kept in mind when evaluating patients with increased liver enzymes. Risk assessment in individuals undergoing treatment with biologicals represents a step towards achieving a personalized medicine approach to identify those patients that will safely benefit from this therapeutic approach. Patients and physicians must be alert of anti-TNF agents as potential causes of drug-induced liver injury and monitor the therapies. Personalizing therapeutic pharmacovigilance promises to optimize benefits while minimizing side effects.


Unprovoked status epilepticus: the prognosis for otherwise normal children with focal epilepsy.
To document the effect of unprovoked status epilepticus (SE) on the prognosis for otherwise normal children with focal epilepsy. From the Nova Scotia Childhood Epilepsy Study (population-based), we identified patients with focal epilepsy, normal intelligence, and neurologic examination and follow-up ≥ 10 years. We compared those with and without unprovoked SE. One hundred eighty-eight cases had a mean follow-up of 27 ± 5 years with no deaths from SE. Thirty-nine (20%) had SE, 19 of whom experienced their first seizure. The number of episodes of SE was 1 in 27 patients (69%) and 2 to 10 in 12 patients. At onset 9 of 39 (23%) SE patients and 35 of 149 (23%) no-SE patients had specific learning disorders. At follow-up, 11 (28%) SE and 49 (33%) no-SE patients had learning disorders (P = not statistically different [ns]). Grades repeated, high school graduation, and advanced education did not differ. The number of antiepileptic drug (AED) used throughout the clinical course was the same: 22/39 (56%). SE patients used ≤ 2 AEDs versus 99 of 149 (64%) no-SE patients (P = .2). The distribution of patients using 3 to 11 AEDs was similar. The remission rate (seizure-free without AEDs at the end of follow-up) for SE patients was 24 of 39 (61%) versus 99 of 149 (66%) in no-SE (P = .5). Intractable epilepsy occurred in 15% SE and 11% of no-SE cases. SE often recurs but apparently has little influence on long-term intellectual and seizure outcome in normally intelligent children with focal epilepsy.


The validity and reliability of a Total Hip Arthroplasty Outcome Evaluation Questionnaire.
The Société Internationale de Chirurgie Orthopédique et de Traumatologie (SICOT), the Task Force on Outcome Studies of The American Academy of Orthopaedic Surgeons, and The Hip Society reached a consensus on the nomenclature to be used for the evaluation of the results of total hip arthroplasty. The Task Force of The American Academy of Orthopaedic Surgeons, to assess the results of total hip arthroplasty from the perspective of the patient, subsequently developed a questionnaire that incorporated this nomenclature. The validity and reliability data regarding this questionnaire are reported in this study. Twenty-five patients participated in the reliability test. The non-response rate was five (0.5 per cent) of 941 possible responses. Test-retest reliability was determined by calculating the Spearman correlation coefficients for each question. The coefficients ranged from 0.41 to 1.0 over a mean test-retest interval of sixteen days. Most items had Spearman coefficients that were greater than 0.50, indicating good or excellent reliability. Validity was assessed, for the fifty-four patients who participated, by calculating the Spearman correlation coefficients for the items regarding pain in the affected hip, limitation of usual activities, capacity for walking without support, and the Sickness Impact Profile. The coefficients ranged from 0.11 (pain and limitation of activity) to 0.56 (Sickness Impact Profile and limitation of activity). These coefficients reflected modest associations, as anticipated, indicating that pain, function, and health status are related yet distinct concepts.(ABSTRACT TRUNCATED AT 250 WORDS)


[Arthroscopic findings concerning rotator cuff lesions and their operative management].
Our objective is to introduce our simplified, easy-to-use classification of rotator cuff (RC) lesions, describe the frequency of individual findings in a considerably large series of shoulder joints examined by arthroscopy, evaluate the results of the operative management of individual lesion types, and recommend optimal surgical approaches. Over the course of 10 years (between October 1st, 2000 and December 31st, 2009), 756 arthroscopic operations on the shoulder joint were performed. RC lesions were identified in 516 cases. We categorized the lesions using our own classification. Patient characteristics were as follows: the mean age was 43 years, 69% of the patients were men, and the right shoulder was affected in 61% of the cases (with the dominant upper limb being affected in 71% of the cases). The patients were followed up for a minimum period of 6 months. All operations were performed in the "beach-chair" position under general anesthesia or in an interscalenic block. The arthroscope was introduced into the shoulder joint through the "soft-spot". Continuous lavage via an arthroscopic pump was used. The glenohumeral joint was examined first; an examination of the subacromial space followed. Once the lesion type was identified, other procedures were performed. In standard situations, type I lesions were managed with ASK sub- acromial decompression (SAD). As to type II lesions, we initially performed open RC reconstruction with acromioplasty, which we later replaced with ASK-assisted RC reconstruction with SAD; we are currently managing these lesions with ASK RC reconstruction + SAD. As for type III lesions, we initially used to treat them with open RC reconstruction with acromio - plasty; we are now performing ASK-assisted RC reconstruction with mini-incision + SAD. We are trying to use "double-row" sutures in certain cases. The initial management of type IV lesions consisted of ASK palliative resection of RC remnants combined with SAD. Currently, we are performing partial muscle transfer of the intact subscapularis muscle tendon (Karas) or partial non-anatomical RC reconstruction (Burkhart). A combination of both methods described above was required in some cases. If delamination of the RC was found, partial reconstruction using the "double-layer" technique took place. Open acromioplasty was added during all operations. Type V lesions are managed with ASK palliative resection of RC remnants + SAD; when this approach proves unsuccessful, which is a rare phenomenon, resurfacing follows. The results were evaluated after 6 months using a modified Constant functional score. Besides clinical examination, self-assessment questionnaires filled in by the patients were also evaluated. Out of a total of 516 RC lesions, type I was the most prevalent (54%), followed by type V (16%). The prevalence of lesion types II, III and IV was about 10% each. In type I, the mean improvement measured by the Constant score was 36 points. As for type II, open reconstruction, ASK-assisted reconstruction and ASK reconstruction resulted in mean improvements of 31, 34, and 35 points, respectively. While open reconstruction of type III lesions was associated with a 27-point improvement on the Constant score, the use of ASK-assisted reconstruction resulted in a 29-point improvement. In type IV, the use of ASK palliative resection of RC remnants, muscle transfer (Karas), partial reconstruction (Burkhart), and a combination of the last two methods led to the mean 19-, 25-, 22-, and 22- point improvements respectively. Following ASK palliative resection, the mean Constant score improvement in type V lesions was 17 points, while the use of resurfacing, if performed, was associated with a 21-point improvement. DISCUSSION In type I lesions, favourable long-term outcomes are achieved through ASK SAD, which removes RC irritation within the narrowed subacromial space. RC reconstruction or sutures, which can be performed arthroscopically quite easily, are indicated in type II lesions. The situation is similar in type III lesions, where, from a technical point of view, reconstruction is facilitated by ASK-assisted reconstruction with mini-incision. Since type IV lesions are the most complex ones, the largest number of surgical management methods is described here. As for muscle transfer, the subscapularis and latissimus dorsi muscles are used most often, the latter requiring wider surgical access. Partial non-anatomical reconstruction is useful, too. New synthetic prostheses, as well as biosynthetic or biologic prostheses prepared with cultures of pluripotent stem cells, have been developed recently. Unlike some other authors, we prefer open surgery. Attempts at ASK reconstruction increase surgical time considerably, while the cosmetic effect is negligible if many ASK ports are used. Reconstruction is contraindicated in type V lesions; good outcomes are being achieved with ASK palliative resection of RC remnants (Apoil). Type I lesions are successfully managed with ASK SAD. The method of choice in type II lesions is ASK reconstruction. In type III lesions, we have been getting good results with ASK-assisted RC reconstruction with mini-incision. As for type IV lesions in older patients, we have good experience with muscle transfer of a part of the intact subscapularis muscle tendon (Karas); partial non-anatomial reconstruction (Burkhart) is deemed more beneficial in younger and more active patients. For anatomical reasons, a combination of both above-mentioned methods had to be used in some cases. ASK palliative resection of RC remnants, rarely followed by resurfacing when unsuccessful, remains the method of choice in treating type V lesions. Key words: shoulder arthroscopy, rotator cuff lesions, classification, subacromial decompression, reconstruction, open surgery, palliative resection, Constant Functional Score.


Pharmacodynamic studies of nitrofurantoin against common uropathogens.
To determine the pharmacokinetic/pharmacodynamic index that best correlates to nitrofurantoin's antibacterial effect, we studied nitrofurantoin activity against common causative pathogens in uncomplicated urinary tract infection (UTI). Five isolates [two Escherichia coli (one isolate producing the ESBL CTX-M-15), two Enterococcus faecium (including one that was vancomycin resistant) and one Staphylococcus saprophyticus] were used. The MICs of nitrofurantoin were determined by Etest. Time-kill curves with different concentrations of nitrofurantoin (based on multiples of isolate-specific MICs) were followed over 24 h. An in vitro kinetic model was used to simulate different time-concentration profiles, exposing E. coli to nitrofurantoin for varying proportions of the dosing interval. The outcome parameters reduction in cfu 0-24 h (Δcfu0-24) and the area under the bactericidal curve (AUBC), were correlated with time over MIC (T>MIC) and area under the antibiotic concentration curve divided by the MIC (AUC/MIC). A bactericidal effect at varying static drug concentrations was achieved for all isolates. All isolates showed similar kill curve profiles. In the kinetic model, the effect of nitrofurantoin on E. coli displayed a 4 log reduction in cfu/mL within 6 h at 8 × MIC. The outcome parameters Δcfu0-24 and AUBC had a good correlation with T>MIC (R ≈ 0.83 and R ≈ 0.67, respectively), whereas log(AUC/MIC) was significantly poorer (R ≈ 0.39 and R ≈ 0.53, respectively). Nitrofurantoin was highly effective against E. coli and S. saprophyticus isolates; the killing effect against E. faecium was not as rapid, but still significant. Against E. coli, nitrofurantoin was mainly associated with a concentration-dependent action; this was confirmed in the kinetic model, in which T>MIC displayed the best correlation.


Hepatoxic alterations induced by inhalation of trichlorethylene (TCE) in rats.
Trichlorethylene (TCE) is one of the most potent organic unsaturated solvents being used in dry cleaning, metal degreasing, thinner for paints varnishes and electroplating, etc. and has been reported to be a hepatoxicant through oral and dermal exposure. However, its inhalation toxicity data is very limited in the literature due to the fact that the exposure levels associated with these effects were usually not reported. Hence, inhalation toxicity study was carried out for hepatotoxic studies. Inhalation toxicity studies was carried out by exposing rats to TCE for 8, 12 and 24 weeks in a dynamically operated whole body inhalation chamber. Sham treated control rats were exposed to compressed air in the inhalation chamber for the same period. Significant increase in liver weight (liver enlargement) appeArance of necrotic lesion with fatty changes and marked necrosis were observed after longer duration (12 and 24 weeks) of TCE exposure. The lysosomal rupture resulted in increased activity of acid and alkaline phosphatase alongwith reduced glutathione content and total increased sulfhydryl content in liver tissue. TCE exposure. through inhalation route induces hepatotoxicity in terms of marked necrosis with fatty changes and by modulating the lysosomal enzymes.


Pharmacokinetics and Acceptability of Subcutaneous Injection of Testosterone Undecanoate.
Can injectable testosterone undecanoate (TU) be administered effectively and acceptably by the subcutaneous (SC) route? To investigate the acceptability and pharmacokinetics (PK) of SC injection of TU. Randomized sequence, crossover clinical study of SC vs IM TU injections. Ambulatory clinic of an academic andrology center. Twenty men (11 hypogonadal, 9 transgender men) who were long-term users of TU. injections. Intervention: Injection of 1000 mg TU (in 4 mL castor oil vehicle) by SC or IM route. Main Outcome Measures: Patient-reported pain, acceptability, and preference scales. PK by measurement of serum testosterone, dihydrotestosterone (DHT), and estradiol (E2) concentrations with application of population PK methods and dried blood spot (DBS) sampling. Pain was greater after SC compared with IM injection 24 hours (but not immediately) after injection but both routes were equally acceptable. Ultimately 11 preferred IM, 6 preferred SC, and 3 had no preference. The DBS-based PK analysis of serum testosterone revealed a later time of peak testosterone concentration after SC vs IM injection (8.0 vs 3.3 days) but no significant route differences in model-predicted peak testosterone concentration (8.4 vs 9.6 ng/mL) or mean resident time (183 vs 110 days). The PK of venous serum testosterone, DHT, and E2 did not differ according to route of injection. We conclude that SC TU injection is acceptable but produces greater pain 24 hours after injection that may contribute to the overall majority preference for the IM injection. The PK of testosterone, DHT, or E2 did not differ substantially between SC and IM routes. Hence whereas further studies are required, the SC route represents an alternative to IM injections without a need to change dose for men for whom IM injection is not desired or recommended.


One instead of two knives for surgical incision. Does it increase the risk of postoperative wound infection?
We evaluated the rate of postoperative wound infection following the use of one or two knives for incision. The infection rate in 277 patients who were operated on with one knife was 3.6%, in 309 patients who were operated on with two knives the rate was 5.5%. This difference was not statistically significant. The limit of a one-sided confidence interval bound from the estimated difference of infection rates in the two groups of patients was 0.94% at a confidence level of 0.95. Thus, if there was any difference at all in favor of two knives with respect to infection, it was probably less than 1%. The present results indicate that the old surgical practice of discarding the skin knife and using a separate scalpel for the deep incision can be abandoned without increasing the risk of wound infection.


[Experiences with capnometry in pediatric intensive care].
We investigated the correlation between arterial and end-tidal pCO2 in 17 children during intensive care. The indications for using capnometry were noninvasive monitoring of ventilation after cardiac surgery or during complicated course of illness or for control of intended hyperventilation. We found a good correlation between arterial and end-tidal pCO2 in the overall patient population (r = 0.82), but the relationship varied widely from patient to patient. There was only a weak correlation (r = 0.44) in pCO2 over 45 mm Hg. Hyperventilation could be identified in 64.2%, whereas hypoventilation was correctly indicated in only 23%.


Predicting Risk of Postoperative Disease Recurrence in Crohn's Disease: Patients With Indolent Crohn's Disease Have Distinct Whole Transcriptome Profiles at the Time of First Surgery.
Assessing risk of Crohn's disease (CD) recurrence following ileocolic resection (ICR) is necessary to optimize medical management and prevent long-term complications. This study aimed to identify noninvasive markers that could predict postoperative disease activity. Inclusion criteria were a diagnosis of CD, first ICR, interval colonoscopy, and whole transcriptome array meeting quality control standards. Demographic and clinical data were obtained from the electronic medical record. RNA extraction and human transcriptome microarray were performed on noninflamed ileal margins from operative specimens. Clinical data and random forest were analyzed in R. Principal components analysis, hierarchical clustering, and pathway enrichment were performed in Partek. Sixty-five patients completed the study, and 5 were excluded from analysis due to extreme variability on whole transcriptome analysis. Unsupervised hierarchical clustering revealed that patients with an i0 Rutgeerts score generally segregated from all others. In anti-TNF-naïve patients, unsupervised hierarchical clustering revealed complete segregation of patients with an i0 score. Reduced escalation in therapy and continued mucosal remission, consistent with indolent disease, were seen in the 4 years following surgery. Random forest identified 30 transcripts differentiating i0 patients from the other groups. Pathway enrichment highlighted toll-like receptor, NOD-like receptor, and TNF signaling. This transcriptome signature did not identify i0 anti-TNF-exposed patients. However, anti-TNF-exposed patients with indolent postoperative courses were found to have a transcriptome signature distinct from those with aggressive disease. Anti-TNF-naïve and -exposed patients have unique expression profiles at the time of surgery, which may offer predictive value in assessing the risk of nonrecurrence. 10.1093/ibd/izy228_video1izy228.video15804852517001.


3D bioprinting dual-factor releasing and gradient-structured constructs ready to implant for anisotropic cartilage regeneration.
Cartilage injury is extremely common and leads to joint dysfunction. Existing joint prostheses do not remodel with host joint tissue. However, developing large-scale biomimetic anisotropic constructs mimicking native cartilage with structural integrity is challenging. In the present study, we describe anisotropic cartilage regeneration by three-dimensional (3D) bioprinting dual-factor releasing and gradient-structured constructs. Dual-factor releasing mesenchymal stem cell (MSC)-laden hydrogels were used for anisotropic chondrogenic differentiation. Together with physically gradient synthetic biodegradable polymers that impart mechanical strength, the 3D bioprinted anisotropic cartilage constructs demonstrated whole-layer integrity, lubrication of superficial layers, and nutrient supply in deep layers. Evaluation of the cartilage tissue in vitro and in vivo showed tissue maturation and organization that may be sufficient for translation to patients. In conclusion, one-step 3D bioprinted dual-factor releasing and gradient-structured constructs were generated for anisotropic cartilage regeneration, integrating the feasibility of MSC- and 3D bioprinting-based therapy for injured or degenerative joints.


Regulation of endothelin-1- and lysophosphatidic acid-stimulated tyrosine phosphorylation of focal adhesion kinase (pp125fak) in Rat-1 fibroblasts.
The characteristics of protein tyrosine phosphorylation were examined in Rat-1 fibroblasts in response to endothelin-1 (ET-1) and 1-oleoyl-lysophosphatidic acid (LPA). Both agonists stimulated the biphasic tyrosine phosphorylation of at least three major proteins of approx. 120 kDa (pp116, pp120 and pp130) and two of 80 kDa (pp80 and pp70). Immunoprecipitation experiments indicated that the pp120 protein corresponded to the recently described focal adhesion protein kinase pp125fak. Phorbol 12-myristate 13-acetate, alone or in combination with the calcium ionophore A23187, also stimulated the phosphorylation of pp125fak but to a smaller extent than LPA or ET-1. Removal of both extracellular and intracellular Ca2+ did not significantly reduce LPA- and ET-1-stimulated tyrosine phosphorylation of pp125fak. In cells where protein kinase C activity was down-regulated or inhibited, ET-1-stimulated tyrosine phosphorylation of pp125fak was reduced to a greater extent than phosphorylation in response to LPA. In addition, ET-1-stimulated tyrosine phosphorylation of pp80 was decreased by 50-70% in response to protein kinase C inhibition at both 2 and 60 min whereas LPA-stimulated tyrosine phosphorylation of this protein was only reduced at 2 min. Pretreatment with pertussis toxin reduced the tyrosine phosphorylation of pp42 and pp44 forms of mitogen-activated protein kinase in response to both ET-1 and LPA but reduced the tyrosine phosphorylation of pp125fak only in response to LPA. These results indicate agonist-specific differences in the regulation of pathways mediating the tyrosine phosphorylation of pp125fak and other target proteins.


Accumulation of plasma triiodothyronine sulfate in rats treated with propylthiouracil.
Triiodothyronine sulfate (T3S) is rapidly deiodinated by the propylthiouracil (PTU)-sensitive type I deiodinase. Here we examined the effects of PTU on plasma T3S levels in rats after intravenous administration of radiolabeled T3 or T3S. Sephadex LH-20 chromatography and high-performance liquid chromatography were used to quantify conjugated and nonconjugated iodothyronines, and iodide was measured as the TCA-soluble radioactivity. In control rats, radioiodide was the main metabolite of both T3 and T3S. Plasma T3S was cleared more rapidly than plasma T3 despite increased binding to plasma proteins. PTU reduced plasma iodide levels by 66 and 78% after T3 and T3S, respectively, and decreased plasma clearance of T3S by 81%. However, PTU had no effect on plasma T3 clearance but increased plasma T3S from injected T3 4.2 times. Biliary excretion of injected T3S was less than 20% in normal rats, in contrast to 70% within 4 h in PTU-treated rats. In conclusion, T3S is an important intermediate in the in vivo metabolism of T3 in rats and accumulates in plasma if type I deiodination is inhibited.


Colorimetric sensing strategy for heparin assay based on PDDA-induced aggregation of gold nanoparticles.
Herein, we report a highly sensitive colorimetric sensor for the detection of heparin based on its anti-aggregation effect of the PDDA-gold nanoparticle colloidal system. PDDA-induced non-crosslinking aggregation of gold nanoparticles is firstly investigated and the phenomenon of heparin mediated color recovery is then observed, which can be used to indicate the concentration of heparin. This method is proved to be highly sensitive and selective. Moreover, it has been successfully applied to determine human blood serum samples, the results of which demonstrate great potential practical utility with simple operations.


Antiplatelet or anticoagulant therapy might not increase the risk of haemoptysis in patients with bronchiectasis.
The aim of this study was to assess whether the use of antiplatelets and anticoagulants increased haemoptysis in patients with bronchiectasis. Cases (n = 242) with a history of haemoptysis were compared with controls (n = 242) without a history of haemoptysis. Of the 242 case patients, 16.5% took antiplatelets compared with 19.8% of controls (P = 0.346). The proportion of warfarin users did not differ between cases and controls (3.3% vs. 2.5%, P = 0.588). The use of these agents might not be associated with increased risk of haemoptysis in patients with bronchiectasis.


Conducting biological research to advance rehabilitation nursing practice.
Rehabilitation nursing practice is concerned with many clinical manifestations that have an underlying biological impairment. Advances in managing these manifestations will depend in part on research that incorporates the biological dimension. The purpose of this article is to encourage more rehabilitation nurses to engage in biological research. To achieve this aim, several different categories of biological nursing research are described using rehabilitation nursing examples, biological measures and approaches are discussed, and possible general clinical outcomes, with examples from previously published biological nursing research, are described. Biological nursing research may enhance professional competence, improve patient care, and improve patient safety.


Antibiotic prophylaxis: different practice patterns within and outside the United States.
Endophthalmitis remains a rare but important cause of visual loss. Prophylaxis strategies are important to reduce rates of endophthalmitis after cataract surgery, intravitreal injection, and other procedures. There is substantial variability between the US and the rest of the world. During cataract surgery, intracameral antibiotics are commonly used in many nations, especially in Europe, but are less commonly used in the US. A randomized clinical trial from the European Society of Cataract and Refractive Surgeons reported an approximately fivefold reduction in endophthalmitis rates associated with intracameral cefuroxime but these results are controversial. There are no randomized clinical trials regarding endophthalmitis associated with intravitreal injection. Topical antibiotics are commonly used in many nations, but are less commonly used in the US. At this time, there is no global consensus and it appears unlikely that additional major clinical trials will conclusively define the optimal endophthalmitis prophylaxis techniques.


The dynamics of brain and cerebrospinal fluid growth in normal versus hydrocephalic mice.
Hydrocephalus has traditionally been quantified by linear measures of ventricular size, with adjunct use of cortical mantle thickness. However, clinical outcome depends on cognitive function, which is more directly related to brain volume than these previous measures. The authors sought to quantify the dynamics of brain and ventricular volume growth in normal compared with hydrocephalic mice. Hydrocephalus was induced in 14-day-old C57BL/6 mice by percutaneous injection of kaolin into the cisterna magna. Nine hydrocephalic and 6 normal mice were serially imaged from age 2-12 weeks with a 14.1-T MR imaging unit. Total brain and ventricle volumes were calculated, and linear discriminant analysis was applied. Two very different patterns of response were seen in hydrocephalic mice compared with mice with normative growth. In one pattern (3 mice) brain growth was normal despite accumulation of CSF, and in the second pattern (6 mice) abnormal brain enlargement was accompanied by increased CSF volume along with parenchymal edema. In this latter pattern, spontaneous ventricular rupture led to normalization of brain volume, implying edema from transmantle pressure gradients. These 2 patterns of hydrocephalus were significantly discriminable using linear discriminant analysis (p < 0.01). In contrast, clinically relevant measurements of head circumference or frontal and occipital horn ratios were unable to discriminate between these patterns. This study is, to the authors' knowledge, the first serial quantification of the growth of brain and ventricle volumes in normal versus hydrocephalic development. The authors' findings demonstrate the feasibility of constructing normative curves of brain and fluid growth as complements to normative head circumference curves. By measuring brain volumes, distinct patterns of brain growth and enlargement can be observed, which are more likely linked to cognitive development and clinical outcome than fluid volumes alone.


Challenging the inbreeding hypothesis in a eusocial mammal: population genetics of the naked mole-rat, Heterocephalus glaber.
The role of genetic relatedness in the evolution of eusociality has been the topic of much debate, especially when contrasting eusocial insects with vertebrates displaying reproductive altruism. The naked mole-rat, Heterocephalus glaber, was the first described eusocial mammal. Although this discovery was based on an ecological constraints model of eusocial evolution, early genetic studies reported high levels of relatedness in naked mole-rats, providing a compelling argument that low dispersal rates and consanguineous mating (inbreeding as a mating system) are the driving forces for the evolution of this eusocial species. One caveat to accepting this long-held view is that the original genetic studies were based on limited sampling from the species' geographic distribution. A growing body of evidence supports a contrary view, with the original samples not representative of the species-rather reflecting a single founder event, establishing a small population south of the Athi River. Our study is the first to address these competing hypotheses by examining patterns of molecular variation in colonies sampled from north and south of the Athi and Tana rivers, which based on our results, serve to isolate genetically distinct populations of naked mole-rats. Although colonies south of the Athi River share a single mtDNA haplotype and are fixed at most microsatellite loci, populations north of the Athi River are considerably more variable. Our findings support the position that the low variation observed in naked mole-rat populations south of the Athi River reflects a founder event, rather than a consequence of this species' unusual mating system.


Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome.
To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.