The association of miR-126-3p, miR-126-5p and miR-664-3p expression profiles with outcomes of patients with metastatic colorectal cancer treated with bevacizumab.
MicroRNAs regulate the expression of genes involved in several important cancer-related processes including cell adhesion, proliferation, and tumour angiogenesis. Bevacizumab is routinely used in the treatment of patients with metastatic colorectal cancer, but, so far, no reliable biomarker predicting response to bevacizumab has been established. The aim of our retrospective study was to evaluate the association of miR-126-3p, miR-126-5p and miR-664-3p tumour expression levels with outcomes of patients with metastatic colorectal cancer treated with bevacizumab. The study included 63 patients. For the assessment of microRNA expression, gene-specific TaqMan assays were used. The median progression-free survival and overall survival for patients with low tumour expression of miR-126-3p were 8.8 and 20.6 months versus 13.5 months and median overall survival was not reached for patients with high expression ( p = 0.0064 and p = 0.0027), respectively. The median progression-free survival and overall survival for patients with low tumour expression of miR-126-5p were 9.0 and 22.2 months versus 12.0 and 23.4 months for patients with high expression ( p = 0.2113 and 0.6858), respectively. The median progression-free survival and overall survival for patients with low tumour expression of miR-664-3p were 9.1 and 22.5 months versus 8.8 and 23.4 months for patients with high expression ( p = 0.2542 and p = 0.1922), respectively. The multivariable Cox proportional hazards model revealed that miR-126-3p expression was significantly associated with progression-free survival (hazard ratio = 0.28, p = 0.0053) and also with overall survival (hazard ratio = 0.18, p = 0.0046). In conclusion, the results of this study suggest that the expression of miR-126-3p in the tumour tissue was associated with outcome of metastatic colorectal cancer patients treated with bevacizumab.


Universal cover-time distribution of heterogeneous random walks.
The cover-time problem, i.e., the time to visit every site in a system, is one of the key issues of random walks with wide applications in natural, social, and engineered systems. Addressing the full distribution of cover times for random walk on complex structures has been a long-standing challenge and has attracted persistent efforts. Usually it is assumed that the random walk is noncompact, to facilitate theoretical treatments by neglecting the correlations between visits. The known results are essentially limited to noncompact and homogeneous systems, where different sites are on an equal footing and have identical or close mean first-passage times, such as random walks on a torus. In contrast, realistic random walks are prevailingly heterogeneous with diversified mean first-passage times. Does a universal distribution still exist? Here, by considering the most general situations of noncompact random walks, we uncover a generalized rescaling relation for the cover time, exploiting the diversified mean first-passage times that have not been accounted for before. This allows us to concretely establish a universal distribution of the rescaled cover times for heterogeneous noncompact random walks, which turns out to be the Gumbel universality class that is ubiquitous for a large family of extreme value statistics. Our analysis is based on the transfer matrix framework, which is generic in that, besides heterogeneity, it is also robust against biased protocols, directed links, and self-connecting loops. The finding is corroborated with extensive numerical simulations of diverse heterogeneous noncompact random walks on both model and realistic topological structures. Our technical ingredient may be exploited for other extreme value or ergodicity problems with nonidentical distributions.


Inhibitory effect of biocides on the viable masses and matrices of Staphylococcus aureus and Pseudomonas aeruginosa biofilms.
Bacteria and matrix are essential for the development of biofilms, and assays should therefore target both components. The current European guidelines for biocidal efficacy testing are not adequate for sessile microorganisms; hence, alternative discriminatory test protocols should be used. The activities of a broad range of biocides on Staphylococcus aureus and Pseudomonas aeruginosa biofilms were evaluated using such in vitro assays. Nearly all selected biocides showed a significant decrease in S. aureus biofilm viability, with sodium hypochlorite and peracetic acid as the most active biocides. Only hydrogen peroxide and sodium hypochlorite showed some inhibitory effect on the matrix. Treatment of P. aeruginosa biofilms was roughly comparable to that of S. aureus biofilms. Peracetic acid was the most active on viable mass within 1 min of contact. Isopropanol ensured a greater than 99.999% reduction of P. aeruginosa viability after at least 30 min of contact. Comparable to results with S. aureus, sodium hypochlorite and hydrogen peroxide markedly reduced the P. aeruginosa matrix. This study clearly demonstrated that despite their aspecific mechanisms of action, most biocides were active only against biofilm bacteria, leaving the matrix undisturbed. Only hydrogen peroxide and sodium hypochlorite were active on both the biofilm matrix and the viable mass, making them the better antibiofilm agents. In addition, this study emphasizes the need for updated and standardized guidelines for biofilm susceptibility testing of biocides.


The structure and spectra of organic peroxy radicals.
Recent spectroscopic and computational work on organic peroxy radicals, RO(2), is reviewed and extended with an emphasis on radicals where R is an alkyl group. Detailed experimental spectral, structural relationships are developed and show the dependence of spectral properties on the number of carbon atoms in the radical, and its isomeric and conformeric structure. These empirical relationships are explored and rationalized with the help of a series of quantum chemistry calculations, which are in turn benchmarked by the experimental data. The application of the spectra as a diagnostic for sensitive and selective measurement of radical concentrations for different RO(2) species in an isomer- and conformer-specific manner is described. Future areas of research including investigation of additional peroxy species and high resolution spectra of cold radicals are discussed.


Ten-Year Experience in the Prevention of Post-Kasai Cholangitis.
Cholangitis is the most common complication after the Kasai procedure. It can be life-threatening and may affect long- and short-term outcomes of children with biliary atresia. We summarize our experiences in the prevention of early-onset cholangitis. From January 2002 to March 2013, children with biliary atresia (BA) who underwent the Kasai procedure in the General Surgical Department were included in a retrospective cohort study. These patients were divided into group A (therapy 1) and group B (therapy 2) depending on the infection prevention protocol and occurrences of cholangitis within the six months after surgery were recorded. Two hundred eighteen children were included in this cohort study. Seventy-six children (35 females and 41 males) were included in group A. One hundred forty-two children (65 females and 77 males) were included in group B. Therapy 1 was our primary protocol and included a third-generation cephalosporin, metronidazole, and human immunoglobulin. Therapy 2 was a modification of therapy 1 that involved imipenem-cilastatin and human immunoglobulin. Statistical analyses were performed. A p value below 0.05 was regarded as significant. In group A, 45 children developed cholangitis within the six months after the Kasai procedure. In group B, 14 of these children experienced post-operative cholangitis. A χ2 analysis was used to examine the difference in the incidence of cholangitis between groups A and B. There was a substantial difference in the morbidity of post-operative cholangitis between groups A and B (59.2% vs. 9.9%, p = 0.000). Cholangitis in the early period after a Kasai procedure can be prevented effectively with an advanced prophylactic protocol.


Role of regulator of G protein signaling proteins in bone.
Regulators of G protein signaling (RGS) proteins are a family with more than 30 proteins that all contain an RGS domain. In the past decade, increasing evidence has indicated that RGS proteins play crucial roles in the regulation of G protein coupling receptors (GPCR), G proteins, and calcium signaling during cell proliferation, migration, and differentiation in a variety of tissues. In bone, those proteins modulate bone development and remodeling by influencing various signaling pathways such as GPCR-G protein signaling, Wnt, calcium oscillations and PTH. This review summarizes the recent advances in the understanding of the regulation of RGS gene expression, as well as the functions and mechanisms of RGS proteins, especially in regulating GPCR-G protein signaling, Wnt signaling, calcium oscillations signaling and PTH signaling during bone development and remodeling. This review also highlights the regulation of different RGS proteins in osteoblasts, chondrocytes and osteoclasts. The knowledge from the recent advances of RGS study summarized in the review would provide the insights into new therapies for bone diseases.


A patient-centred approach to assisted personal body care for patients hospitalised with chronic obstructive pulmonary disease.
To explore the patients' experiences of receiving patient-centred personal body care and to document changes compared to the patients' experiences in previous hospital stays. Patients with severe chronic obstructive pulmonary disease suffer from breathlessness. Personal body care is therefore often a major challenge, and during exacerbation these patients may need comprehensive assistance. The quality of assisted personal body care depends largely on the patients' and the nurses' symptom recognition, disease management and ability to achieve therapeutic clarity in the nurse-patient interaction. We developed, implemented and evaluated a patient-centred approach to assisted personal body care in which these characteristics were sought. The study is a qualitative outcome analysis with an interpretive description methodology. Nine female and two male hospitalised patients with severe chronic obstructive pulmonary disease were selected for patient-centred care. Specially trained nurses and nursing assistants performed the patient-centred personal body care. Data material was obtained through participant observation of body care sessions with the patients, followed by individual in-depth interviews. The transcribed interviews were analysed and an interpretive description of the patients' experiences was established. All patients experienced the patient-centred care to be different from what they had previously experienced. The most fundamental change was the experience of being an active part of a shared project. This experience encompassed three dimensions: clear signs of acknowledgement, attentive time and security. Patient-centred assistance enables patients to take an active part in their personal body care activity. The intervention may be a method for nursing staff to secure patients-centred care. Effective communication, tools for the assessment of breathlessness, clear and straight forward organisation of body care sessions, awareness of pauses and personal acknowledgment are important for the patients' ability to take part in personal body care activities.


Hydroxymethyl lysine is a source of bioavailable lysine for ruminants.
Experiments were conducted to evaluate the availability to ruminants of lysine from hydroxymethyl lysine, a product potentially resistant to ruminal degradation yet able to release free lysine when subjected to the acidic environment of the abomasum. An in vitro ruminal fermentation assay that led to ammonia production from free lysine was used for initial assessments, but the hydroxymethyl lysine was inhibitory to lysine degradation at the concentrations tested in vitro; therefore, an in vivo assay with sheep, using plasma lysine concentrations as the response criterion, was used for assessment. twelve mature sheep were fed graded amounts of lysine from either a commercially available ruminally protected lysine product with known availability or from hydroxymethyl lysine. the protected lysine product provided 3 or 6 g/d of metabolizable lysine, whereas the hydroxymethyl lysine provided 3 or 6 g/d of total lysine. Plasma lysine concentrations increased linearly in response to both the ruminally protected lysine product and hydroxymethyl lysine. by slope ratio analysis, the bioavailability of lysine in hydroxymethyl lysine was estimated to be 94% of that for the commercially available product. We concluded that hydroxymethyl lysine may be used as an effective means of supplementing lysine to ruminants.


The ferroelectric and cubic phases in BaTiO3 ferroelectrics are also antiferroelectric.
Using quantum mechanics (QM, Density Functional Theory) we show that all four phases of barium titanate (BaTiO(3)) have local Ti distortions toward 111 (an octahedral face). The stable rhombohedral phase has all distortions in phase (ferroelectric, FE), whereas higher temperature phases have antiferroelectric coupling (AFE) in one, two, or three dimensions (orthorhombic, tetragonal, cubic). This FE-AFE model from QM explains such puzzling aspects of these systems as the allowed Raman excitation observed for the cubic phase, the distortions toward 111 observed in the cubic phase using x-ray fine structure, the small transition entropies, the heavily damped soft phonon modes, and the strong diffuse x-ray scattering in all but the rhombohedral phase. In addition, we expect to see additional weak Bragg peaks at the face centers of the reciprocal lattice for the cubic phase. Similar FE-AFE descriptions are expected to occur for other FE materials. Accounting for this FE-AFE nature of these phases is expected to be important in accurately simulating the domain wall structures, energetics, and dynamics, which in turn may lead to the design of improved materials.


A Comparative Study of Health Disparities in Cervical Cancer Mortality Rates Through Time Between Black and Caucasian Women in Alabama and the US.
The main purpose of this study was to assess changes in cervical cancer mortality rates through time between Black and Caucasian women residing in Alabama and the US. Alabama cervical cancer mortality rates (MR), percentage differences, percentage changes and annual percentage changes for trends were compared with the US baseline and target rates. The US Baseline data and target objectives of utilization of cervical cancer screening and MR were obtained from Healthy People 2020. The cervical cancer behavioral risk factors and utilization of screening tests data were obtained from CDC's Behavioral Risk Factor Surveillance System (BRFSS). The cervical cancer MR data were obtained from the Surveillance, Epidemiology, and End Results (SEER). The analysis was done using SEER*Stat and Linear Trendlines analysis. Although Blacks in Alabama had higher cervical cancer MR through times, a decreasing trend was noted for both races. However, in Alabama, there is no significant change in Blacks aged 65 years and older in cervical cancer MR, despite a high screening rate compared to Whites. In contrast, between 2002 and 2012, Whites in Alabama and the US made a significant progress toward the Healthy People 2020 goal. In Alabama, there exists cervical cancer MR disparity in Blacks despite the higher rates of screening for cervical cancer as would otherwise be expected. The state has not yet achieved the Healthy People 2020 goal. Public health officials should monitor progress toward reduction and/or elimination of these disparities by focusing in a follow up of screening.


A new dimethyl sulfoxide-based method for gene promoter methylation detection.
The identification of gene promoter methylation is a useful tool for the molecular diagnosis of human diseases. We have developed a new PCR-based technique for detecting the methylation status of CpG islands of gene promoters. This new method, named methyl-sensitive dimethyl sulfoxide-PCR (Ms-DMSO-PCR), is based on the finding that methylated and unmethylated DNAs show a different sensitivity to the amount of DMSO used in the PCR reaction. For the amplification of methylated DNA, more DMSO is required in comparison to unmethylated DNA. This finding resulted in the development of a simple PCR screening of CpG islands with addition of DMSO in the range from 0 to 8% (v/v), and the same pair of primers is sufficient for distinguishing hyper- or hypomethylated gene promoters from normally methylated sequences. This new technique is a one-step procedure and does not require any modifications of DNA or expensive equipment. Therefore, Ms-DMSO-PCR has the potential to be widely used for clinical applications as well in basic research.


Substance use and addictive behaviours during COVID-19 confinement measures increased in intensive users: Results of an online general population survey in the Czech Republic.
The COVID-19 pandemic has affected substance use and other addictive behaviour, however detailed insight is lacking. Online questionnaire survey on the sample of 3,000 respondents aged 15+ randomly selected from the Czech internet panel using socio-demographic quotas was performed shortly after the end of confinement measures in May 2020 (response rate 35.4%). Questions covered current prevalence and patterns of substance use (i.e. in the last 12 months) and other forms of addictive behaviours as well as changes in their behaviour during the confinement measures. Responses were provided on categorical scale; a factor of 0 to 2 was assigned to the categories to quantify the changes where 1 means no change. Respondents reporting the highest frequency of current use, especially the use of alcohol, cannabis and sedatives, further increased their intensity of use during the confinement measures by 5-10% on average, while less frequent users reduced it. The reduction of use during confinement measures increased with decreasing frequency of current use. Although the same correlation exists in tobacco smokers, decrease in intensity of use was observed also in daily smokers. On the population level, our results suggest a slight increase in total alcohol and sedatives consumption and a significant increase in the total consumption of gaming and social media. On the contrary, there was a significant reduction in the consumption of tobacco and online gambling (likely due to the ban on sports matches), and a slight reduction in the consumption of cannabis and other illicit drugs. People with intensive patterns of substance use increased their use during confinement measures. The same concerns gaming and social media. Without this insight the overall picture suggests rather overall reduction of consumption. Addiction treatment system should prepare for the increase of treatment demand following COVID-19 epidemic.


Potential Mediators of Load-Related Changes in Movement Complexity in Young, Healthy Adults.
Movement screening has become increasingly popular among tactical professionals. This popularity has motivated the design of interventions that cater to improving outcomes on the screens themselves, which are often scored in reference to an objective norm. In contrast to the assumptions underlying this approach, dynamical systems theory suggests that movements arise as a function of continuously evolving constraints and that optimal movement strategies may not exist. To date, few data address behavioral complexity in the fundamental movement tasks commonly used in clinical screenings. To provide evidence of complex variability during movement screens and test the role of modifiable-that is, trainable-constraints in mediating loss of complexity during experimental-task manipulations. Crossover study. Research laboratory. Twenty-five male (age = 23.96 ± 3.74 years, height = 178.82 ± 7.51 cm, mass = 79.66 ± 12.66 kg) and 25 female (age = 22.00 ± 2.02 years, height = 165.40 ± 10.24 cm, mass = 63.98 ± 11.07 kg) recreationally active adults. Participants performed tests of balance, range of motion, and strength. Additionally, they performed cyclical movement tasks under a control (C) condition and while wearing an 18.10-kg weight vest (W). Ground reaction forces were sampled at 1000 Hz and used to calculate center of pressure during cyclical movement tests. Multivariate multiscale entropy (MMSE) for the center-of-pressure signal was then calculated. Condition effects (C versus W) were analyzed using paired t tests, and penalized varying-coefficients regression was used to identify models predicting entropy outcomes from balance, range of motion, and strength. The MMSE decreased during the W condition (MMSEC > MMSEW; t49 range = 3.17-5.21; all P values < .01). Moderate evidence supported an association between modifiable constraints and behavioral complexity, but a role in mediating load-related loss of complexity was not demonstrated.


Sonographic patterns of lung consolidation in mechanically ventilated patients with and without ventilator-associated pneumonia: a prospective cohort study.
Thoracic ultrasound (TUS) has been successfully used in the diagnosis of community-acquired pneumonia. Little is known about its diagnostic potential in ventilator-associated pneumonia (VAP). The purpose of this study was to systematically describe the morphology and temporal changes of sonographic patterns in mechanically ventilated patients and to evaluate the diagnostic performance characteristics of TUS-based VAP diagnoses. Patients who were placed on invasive ventilation for reasons other than pneumonia and who were considered at risk for the development of VAP received daily TUS examinations while being closely monitored for the development of pneumonia. Fifty-seven patients were studied. The incidence of VAP was 21.1%. Sonographic patterns of reduced or absent lung aeration were found in 64.2% of examinations. The sonographic pattern of lung consolidation with either dynamic or static air bronchograms was 100% sensitive and 60% specific for VAP in those patients who developed clinical signs and symptoms compatible with pneumonia. The pretest and posttest probabilities were 0.38 and 0.6, respectively. Sonographic patterns of abnormal aeration are frequently observed in mechanically ventilated patients. If sonographic lung consolidation with either static or dynamic air bronchograms is absent, VAP is highly unlikely. The presence of these sonographic patterns in patients with signs and symptoms suggestive of pneumonia significantly increases the probability of VAP.


Vanadate stimulates bone cell proliferation and bone collagen synthesis in vitro.
We recently proposed a hypothesis for the molecular mechanism of the osteogenic action of fluoride in which it stimulates osteoblast proliferation via the inhibition of an osteoblastic acid phosphatase-like phosphotyrosyl protein phosphatase activity. To test this hypothesis, we investigated whether orthovanadate, a known phosphotyrosyl protein phosphatase inhibitor, would mimic fluoride in the stimulation of bone cell proliferation and bone collagen synthesis in vitro. Orthovanadate inhibited the osteoblastic acid phosphatase activity and stimulated bone cell proliferation at the same low concentrations (i.e. 5-15 microM). At the mitogenic doses, orthovanadate also showed a dose-dependent increase in alkaline phosphatase (a marker of mature osteoblasts) in cultured calvarial cells and stimulated bone collagen synthesis, as measured by the incorporation of [3H]proline and the conversion into [3H] hydroxyproline in organ calvaria cultures. Therefore, orthovanadate stimulated bone formation by increasing the number of mature osteoblasts mediated via stimulation of cell proliferation and differentiation. Orthovanadate was dependent on the presence of a mitogen in cell medium for its mitogenic action in vitro and synergistically potentiated the mitogenic actions on osteoblasts of those growth factors, i.e. insulin, epidermal growth factor, insulin-like growth factor I, and skeletal growth factor, whose mitogenic action involved tyrosyl protein phosphorylation. However, the interaction between orthovanadate and basic fibroblast growth factor, a growth factor that does not appear to involve tyrosyl protein phosphorylation, on bone cell proliferation was additive. In summary, these data are consistent with the hypothesis that inhibition of the osteoblastic phosphotyrosyl protein phosphatases can prolong and/or potentiate the mitogenic actions of growth factors, and thereby stimulates cell proliferation.


Kinetics of ethanol production during the reactor feeding phase in constant feb-batch fermentation of molasses.
During the fermentor feeding phase in constant fed-batch ethanol fermentation of molasses, the ethanol production rates are constant and are correlated to the sugar feeding rates by a Monod-like equation. The parameters of this Monod-like correlation depend on the sugars concentration of the feeding mash. A model is proposed to explain the constancy of the ethanol production rate experimentally observed. From the Monod-like correlation it is possible to evaluate the maximum value of the mash feeding rate to be used in order to have a completely fermented medium just at the end of the feeding phase.


Arylation of Cyclopropanol with Pyrrole: Asymmetric Synthesis of Indolizidine 167B, Indolizidine 209D, and Monomorine I.
A Fe(NO3)3-mediated ring-opening arylation of cyclopropanol with the electron-rich pyrrole has been developed, which might proceed through oxidative radical ring opening of cyclopropanol followed by cyclization to the pyrrole motif and then aromatization. This method enables direct arylation of cyclopropanol without prefunctionalization and thus allows rapid access to a diverse array of chiral 5,6,7,8-tetrahydroindolizines from easily available chiral amino acid esters. The synthetic utility has been demonstrated by the asymmetric synthesis of alklaoids (-)-indolizidine 167B, (+)-indolizidine 209D, (+)-monomorine I, and a natural product analogue.


[Effects of modified liangge powder contained serum on LPS stimulated TLR4 expression and release of cytokines in mouse platelets].
To observe the effects of Modified Liangge Powder (MLP) on the expressions of platelet toll like receptor 4 (TLR4) and the release of platelet-derived cytokines interleukin 8 (IL-8), beta platelet globulin (beta-TG), soluble CD40 ligand (sCD40L). The modulating effects on the release of cytokines from mice platelets by TLR4 ligand through monoclonal antibody blocking TLR4 on platelet were compared. The stimulated platelet by LPS was incubated with low (0.94 g/mL), medium (1.89 g/mL), and high (2.84 g/mL) dose of MLP contained serum. The changes of the platelet TLR4 expression and platelet-derived cytokines were observed. The positive expression rate of platelet TLR4 obviously decreased (P < 0.01) and the release of sCD40L and beta-TG from platelets significantly increased (P < 0.01) after stimulated by LPS. However, the release of sCD40L and beta-TG from platelets obviously decreased by TLR4 monoclonal antibody (P < 0.05, P < 0.01). There was no statistical difference in IL-8 between before and after LPS stimulation (P > 0.05). Platelet TLR4 positive expression rate was significantly higher after incubated by medium and high doses of MLP contained serum (P < 0.01), and the releasing of sCD40L and beta-TG was lower in the serum contained groups. The inhibitory effects were enhanced in a dose-dependent manner. LPS induced platelet activation by TLR4 and released sCD40L and beta-TG, while the release of platelet IL-8 was not dependent on platelet TLR4-LPS pathway. MLP could inhibit LPS-stimulated sCD40L and beta-TG, inhibit the binding of platelet TLR4 and LPS in a dose-dependent manner, thus reducing the release of platelet cytokines.


Particle generation, transport, and characterization at the First International Workshop on light absorption by aerosol particles.
Aerosol particles with a wide range of light absorption properties were generated, transported, and characterized to permit meaningful intercomparisons of all the major types of light absorption instruments. The particles were generated in concentrations of ~1 mg m(-3) and 50 microg m(-3) for periods up to 2 h. The particle characteristics ranged from highly absorbing carbonaceous to nearly transparent ammonium sulfate, from submicron ammonium sulfate to supermicron Arizona road dust, and from spherical ammonium sulfate to chain-aggregate carbonaceous and irregular ambient particles.


Immediate effect of three yoga breathing techniques on performance on a letter-cancellation task.
The effects of three yoga breathing practices were evaluated on performance on a letter-cancellation task which is a left-hemisphere dominant task. The three yoga breathing practices (right, left, and alternate nostril breathing) were selected because unilateral forced nostril breathing stimulates the contralateral hemisphere. There were 20 male volunteers whose ages ranged from 20 to 45 years (M age=28.4 yr., SD=5.7). All subjects were assessed before and after four sessions, i.e., right nostril yoga breathing, left nostril yoga breathing, alternate nostril yoga breathing, and breath awareness as a control. The letter-cancellation task scores were significantly improved, i.e., there were fewer errors following right and alternate nostril yoga breathing (Wilcoxon paired signed-ranks test). The improved performance may be related to the enhancement of contralateral hemisphere function found with selective nostril breathing.


Impact of intravesical therapy for non-muscle invasive bladder cancer on the accuracy of urine cytology.
Urine cytology remains an essential diagnostic tool in the surveillance of patients with non-muscle invasive bladder cancer (NMIBC). The correlation of urine cytology with biopsy specimens to determine its accuracy following induction intravesical therapy has not been investigated. A retrospective review was performed of patients who underwent intravesical therapy for biopsy-proven non-muscle invasive disease between 2013 and 2016 at our institution. All patients uniformly underwent cytology and systematic bladder biopsies in the operating room within 12 weeks following intravesical therapy. The accuracy of urinary cytology in predicting high-grade disease recurrence following intravesical therapy was confirmed by correlating cytology results to post-treatment systematic biopsies, regardless of endoscopic findings. Only patients with complete information regarding urine cytology and pathologic biopsy results, both pre- and post-intravesical therapy, were included. 90 cytology samples following intravesical therapy were analyzed from 76 patients who met inclusion criteria. 72 (80.0%) and 18 (20.0%) of the samples were collected from patients initially treated for high- and low-grade disease, respectively. Fifty-six (62.2%) specimens were obtained from patients following induction of bacillus Calmette-Guerin (BCG) therapy; the remainder were from patients treated with intravesical gemcitabine/docetaxel, mitomycin, or BCG/interferon. For patients treated with BCG, cytology was positive for high-grade disease in 8/15 patients with high-grade pathology on follow-up biopsy, thus demonstrating a sensitivity of 53% (95% CI 27-79%), specificity of 95% (95% CI 84-99%), positive predictive value of 80% (95% CI 44-98%), and negative predictive value of 85% (95% CI 71-94%). If cytologic interpretation was broadened to include high-grade and "suspicious for high-grade" findings, sensitivity increased to 67% (95% CI 38-88%) and specificity decreased to 88% (95% CI 74-96%). While urinary cytology maintains a high specificity following intravesical therapy, it demonstrates a low sensitivity for potentially aggressive high-grade urothelial carcinoma. Further evaluation of more effective, clinic-based enhanced cystoscopy techniques and biomarkers is warranted to better identify patients at risk for disease recurrence following BCG therapy.


Infrared spectrometry.
A brief history of the early work on Fourier spectroscopy at the Johns Hopkins University is given as well as a general description of the techniques of Fourier and Hadamard transform spectroscopy. The techniques of tunable diode laser spectroscopy and the difference frequency technique for IR spectral studies are also briefly described including some of their characteristics.


Irrigation pressure and vessel injury during microsurgery: a qualitative study.
Irrigation solution is routinely used in microsurgery. While the anticoagulation solution may aid in anastomotic patency, the direct effect of pressure irrigation can have a detrimental effect on the vessel. An experimental study was performed to determine the effect of irrigation pressure on the vessel wall. Histological evaluation with hematoxylin and eosin (H&E) stain and scanning electron microscopy (SEM) was performed on the arteries of New Zealand white rabbits irrigated with lactated Ringer's solution at pressures of 80 mmHg, 100 mmHg, and 500 mmHg. H&E staining and SEM microscopy demonstrated injury to the endothelial cells and internal elastic lamina at pressures of 100 mmHg or greater. Controlling microsurgical irrigation pressure to less than 100 mmHg may help to avoid vessel injury.


Coping Strategies in Patients Who Had Suicide Attempts.
The aim of this study was to investigate coping strategies suggested to be a determinant of suicide attempt and to compare them with coping strategies of healthy volunteers. This study was conducted on 50 patients who had suicide attempts within the past two months and 52 healthy volunteers who did not have any suicide attempt. They were evaluated with the Turkish version of COPE inventory. The results were analyzed using SPSS version 15.0 for Windows. In the suicide attempt group, 'active coping', 'planning', 'positive reinterpretation and growth' scores were found to be lower than that in the control group. On the other hand, 'restraint coping', 'acceptance', 'focus on and venting of emotions', 'behavioral disengagement', 'substance use' and nonfunctional coping total points were significantly higher in the suicide attempt group. The patients with depression in the suicide group were found less of the 'positive reinterpretation and growth' but more of the 'substance use' compared to the healthy group. Subjects who attempted suicide more than once tended to 'substance use' rather than 'active coping'. 'Focus on and venting of emotions' scores in suicide attempters were higher in women than in males. We observed that individuals who attempted suicide have fewer functional coping strategies and more nonfunctional coping strategies than who do not attempt suicide. It was determined that under stressful situations, individuals with depression tended to alcohol and substance abuse instead of positive reinterpretation and growth. In subjects who had recurrent suicidal attempts, alcohol and substance abuse was more common than active coping. Women were using focusing on and venting of emotions techniques much more than men. We assume that to monitor, and in case of necessity, to change the coping strategies in suicide attempters are vitally important for preventing suicide attempts.


Sorghum bicolor's transcriptome response to dehydration, high salinity and ABA.
Genome wide changes in gene expression were monitored in the drought tolerant C4 cereal Sorghum bicolor, following exposure of seedlings to high salinity (150 mM NaCl), osmotic stress (20% polyethylene glycol) or abscisic acid (125 microM ABA). A sorghum cDNA microarray providing data on 12,982 unique gene clusters was used to examine gene expression in roots and shoots at 3- and 27-h post-treatment. Expression of approximately 2200 genes, including 174 genes with currently unknown functions, of which a subset appear unique to monocots and/or sorghum, was altered in response to dehydration, high salinity or ABA. The modulated sorghum genes had homology to proteins involved in regulation, growth, transport, membrane/protein turnover/repair, metabolism, dehydration protection, reactive oxygen scavenging, and plant defense. Real-time PCR was used to quantify changes in relative mRNA abundance for 333 genes that responded to ABA, NaCl or osmotic stress. Osmotic stress inducible sorghum genes identified for the first time included a beta-expansin expressed in shoots, actin depolymerization factor, inositol-3-phosphate synthase, a non-C4 NADP-malic enzyme, oleosin, and three genes homologous to 9-cis-epoxycarotenoid dioxygenase that may be involved in ABA biosynthesis. Analysis of response profiles demonstrated the existence of a complex gene regulatory network that differentially modulates gene expression in a tissue- and kinetic-specific manner in response to ABA, high salinity and water deficit. Modulation of genes involved in signal transduction, chromatin structure, transcription, translation and RNA metabolism contributes to sorghum's overlapping but nonetheless distinct responses to ABA, high salinity, and osmotic stress. Overall, this study provides a foundation of information on sorghum's osmotic stress responsive gene complement that will accelerate follow up biochemical, QTL and comparative studies.


Risk of Bronchial Complications After Lung Transplantation With Respiratory Corynebacteria. Results From a Monocenter Retrospective Cohort Study.
Corynebacterium spp. are associated with respiratory infections in immunocompromised hosts. A link with bronchial complications after lung transplantation (LTx) has been suggested. We aimed to assess the link between respiratory sampling of Corynebacterium spp. and significant bronchial complication (SBC) after LTx. We performed a single center retrospective study. Inclusion of LTx recipients with at least one respiratory Corynebacterium spp. sample (July 2014 to December 2018). Subjects were matched to unexposed LTx recipients. Primary outcome was SBC occurrence after Corynebacterium spp. isolation. Secondary outcomes were Corynebacterium spp. persistent sampling, chronic lung allograft dysfunction (CLAD) onset and all-cause mortality. Fifty-nine patients with Corynebacterium spp. sampling with 59 without isolation were included. Corynebacterium spp. identification was not associated with SBC occurrence (32.4% vs. 21.6%, p = 0.342). Previous SBC was associated with further isolation of Corynebacterium spp. (OR 3.94, 95% CI [1.72-9.05]). Previous SBC and corticosteroids pulses in the last 3 months were the only factors associated with increased risk of Corynebacterium spp. isolation in multivariate analysis. Corynebacterium spp. sampling was significantly associated with CLAD onset (27.1% vs. 6.9%, p = 0.021). Corynebacterium spp. isolation was not associated with SBC but with higher risk of CLAD. Whether CLAD evolution is affected by Corynebacterium spp. eradication remains to be investigated.


Clinical characteristic and intraoperative findings of uterine perforation patients in using of intrauterine devices (IUDs).
Intrauterine devices (IUDs) are the most popular form of contraception used worldwide; however, IUD is not risk-free. IUD migrations, especially uterine perforations, were frequently occurred in patients. The aim of this study was to investigate the clinical characteristics and intraoperative findings in patients with migrated IUDs. 29 cases of uterine perforation associated with migrated IUDs and 69 control patients were followed between January 2008 to March 2015. Patients who used IUDs within first 6 months from the last delivery experienced a characteristically high rate of the perforation of the uterine wall. A significantly larger number of IUD insertion associated with uterine perforation were performed in rural hospitals or operated at a lower level health care system. There was no clear difference in the age and presented symptoms in patients between two groups. Majority of contraceptive intrauterine devices was the copper-releasing IUDs. Furthermore, patients who used V-shaped IUD showed significantly higher incidence of pelvic adhesions when compared with the users of O-shaped IUDs. Unique clinical characteristics of IUD migration were identified in patients with uterine perforation. Hysteroscopy and/or laparoscopy were the effective approaches to remove the migrated IUDs. Improving operating skills is required at the lower level of health care system.


Wave aberrations in rhesus monkeys with vision-induced ametropias.
The purpose of this study was to investigate the relationship between refractive errors and high-order aberrations in infant rhesus monkeys. Specifically, we compared the monochromatic wave aberrations measured with a Shack-Hartman wavefront sensor between normal monkeys and monkeys with vision-induced refractive errors. Shortly after birth, both normal monkeys and treated monkeys reared with optically induced defocus or form deprivation showed a decrease in the magnitude of high-order aberrations with age. However, the decrease in aberrations was typically smaller in the treated animals. Thus, at the end of the lens-rearing period, higher than normal amounts of aberrations were observed in treated eyes, both hyperopic and myopic eyes and treated eyes that developed astigmatism, but not spherical ametropias. The total RMS wavefront error increased with the degree of spherical refractive error, but was not correlated with the degree of astigmatism. Both myopic and hyperopic treated eyes showed elevated amounts of coma and trefoil and the degree of trefoil increased with the degree of spherical ametropia. Myopic eyes also exhibited a much higher prevalence of positive spherical aberration than normal or treated hyperopic eyes. Following the onset of unrestricted vision, the amount of high-order aberrations decreased in the treated monkeys that also recovered from the experimentally induced refractive errors. Our results demonstrate that high-order aberrations are influenced by visual experience in young primates and that the increase in high-order aberrations in our treated monkeys appears to be an optical byproduct of the vision-induced alterations in ocular growth that underlie changes in refractive error. The results from our study suggest that the higher amounts of wave aberrations observed in ametropic humans are likely to be a consequence, rather than a cause, of abnormal refractive development.


Preliminary studies on the usefulness of medaka, Oryzias latipes, embryos in carcinogenicity testing.
Medaka (Oryzias latipes) embryos were exposed continuously for 10 days to diethylnitrosamine (DENA) at concentrations of 25, 50, or 100 ppm. Following exposure and after hatching, the embryos were placed in clean, carcinogen-free water. Fish were sampled for pathological examination after 1 month, 3, and 6 months. Grossly visible liver tumors were evident after 3 months in 10 and 30% of the fish treated with 50 and 100 ppm DENA, respectively. Following 6 months exposure, 4% of the fish treated with 25 ppm, 15% of those given 50 ppm, and 43% of those treated with 100 ppm DENA contained liver tumors. Focal areas consisting of 10 to 40 highly basophilic cells in the liver were noted at all the exposure concentrations. The incidence of the focal areas increased proportionately with the concentration of DENA and the age of the fish. Liver tumors were examined by light and electron microscopy. Most of the hepatic tumors were moderate to well-differentiated trabecular hepatomas, although 2 cholangiomas and 2 poorly differentiated hepatomas were noted. No liver lesions or tumors were observed in controls.


Comparison of Ki-67 equivalent antibodies.
To compare commercially available Ki-67 equivalent antibodies with regard to qualitative and quantitative immunohistochemical staining characteristics. The following antibodies were used: monoclonal MIB-1 (Immunotech), monoclonal MM1 (Novocastra), polyclonal NCL-Ki-67p (Novocastra), and polyclonal Rah Ki-67 (Dako). All immunostainings were evaluated in squamous epithelium from formalin fixed and paraffin wax embedded pharyngeal tonsils. Labelling indices (LIs) were recorded twice to test their reproducibility. By application of all four antibodies the nuclear staining could be either diffuse, granular, or a combination of both (classified as granular in this study). The diffuse pattern generally showed a strong or moderate staining intensity, whereas the granular pattern displayed a continuum from strong to very weak, making it difficult to discriminate between positive and negative nuclei. The diffuse staining pattern was seen in approximately 59% of the nuclei with the MIB-1 antibody and in 35-45% when the other antibodies were used. The following mean LIs were recorded: MIB-1, 31%; NCL-Ki-67p, 21%; Rah Ki-67, 17%; and MM1, 14%. The reproducibility was excellent for all four antibodies, with the mean of differences between the two runs of counts ranging from 1.1% to 1.5%. The four tested Ki-67 equivalent antibodies revealed differences in qualitative and quantitative staining characteristics, which resulted in considerable variations in registered LIs. The MIB-1 antibody appears to have a higher sensitivity for detecting the Ki-67 antigen than the other three tested antibodies. These differences are important to consider when proliferative activity is determined by the Ki-67 LI.


Characterisation and mapping of adult plant stripe rust resistance in wheat accession Aus27284.
A new adult plant stripe rust resistance gene, Yr80, was identified in a common wheat landrace Aus27284. Linked markers were developed and validated for their utility in marker-assisted selection. Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is among the most important constraints to global wheat production. The identification and characterisation of new sources of host plant resistance enrich the gene pool and underpin deployment of resistance gene pyramids in new cultivars. Aus27284 exhibited resistance at the adult plant stage against predominant Pst pathotypes and was crossed with a susceptible genotype Avocet S. A recombinant inbred line (RIL) population comprising 121 lines was developed and tested in the field at three locations in 2016 and two in 2017 crop seasons. Monogenic segregation for adult plant stripe rust response was observed among the Aus27284/Avocet S RIL population and the underlying locus was temporarily designated YrAW11. Bulked-segregant analysis using the Infinium iSelect 90K SNP wheat array placed YrAW11 in chromosome 3B. Kompetitive allele specific PCR (KASP) primers were designed for the linked SNPs and YrAW11 was flanked by KASP_65624 and KASP_53292 (3 cM) proximally and KASP_53113 (4.9 cM) distally. A partial linkage map of the genomic region carrying YrAW11 comprised nine KASP and two SSR markers. The physical position of KASP markers in the pseudomolecule of chromosome 3B placed YrAW11 in the long arm and the location of markers gwm108 and gwm376 in the deletion bin 3BL2-0.22 supported this conclusion. As no other stripe rust resistance locus has been reported in chromosome 3BL, YrAW11 was formally designated Yr80. Marker KASP_ 53113 was polymorphic among 94% of 81 Australian wheat cultivars used for validation.


Autoregulation of blood flow in renal medulla of the rat: no role for angiotensin II.
Autoregulation of blood flow was assessed by a dual-slit technique in descending and ascending vasa recta of the exposed renal papillae of antidiuretic rats. There was complete autoregulation of blood flow in descending vasa recta. The lower limit of autoregulation was approximately 85 mmHg (1 mmHg = 133.3 Pa) and the upper limit was greater then 160 mmHg. Autoregulation in ascending vasa recta was also good. To test the role of angiotensin II in this autoregulation, the converting enzyme inhibitor captopril was infused. Captopril had no effect on autoregulation of blood flow in either descending or ascending vasa recta. We conclude that blood flow in vasa recta of renal medulla is efficiently autoregulated and that this autoregulation is independent of angiotensin II.


Occurrence of Virulence Genes among Methicillin-Resistant Staphylococcus aureus Isolated from Subclinical Bovine Mastitis.
The occurrence of Staphylococcus aureus-induced subclinical mastitis holds significant implications for public health. This specific microorganism possesses a wide array of pathogenic factors that enable it to adhere to, colonize, invade, and infect the host. The objective of the current study was to assess the prevalence of S. aureus, determine antimicrobial resistance patterns, and identify virulence genes of methicillin-resistant S. aureus (MRSA) strains responsible for subclinical mastitis in bovines. A total of 249 milk samples were collected from various farms in the district of Faisalabad. The presence of subclinical mastitis was assessed by using the California mastitis test. Positive milk samples (n = 100) were then subjected to standard microbiological techniques for isolation and identification of S. aureus. Antibiogram analysis was conducted by using the disc diffusion method to assess antimicrobial resistance. For the molecular detection of S. aureus and its virulence genes, the polymerase chain reaction (PCR) was performed with species-specific primers. The overall prevalence of S. aureus was found to be 40% (40/100), which was confirmed through molecular detection of the nuc gene in 40/40 (100%) of samples using PCR. Antimicrobial susceptibility tests indicated the highest susceptibility to vancomycin, sulfamethoxazole/trimethoprim, erythromycin, gentamicin, ciprofloxacin, and chloramphenicol, while the highest resistance rate was observed against tetracycline. Additionally, 30% of samples (12/40) tested positive for methicillin resistance. PCR analysis revealed that 100% of MRSA-tested isolates harbored the mecA and clfA genes. Furthermore, the MRSA isolates showed the presence of pvl, hla, hlb, sec, icaA, icaD, icaB, and icaC genes at rates of 92, 75, 67, 42, 42, 75, 8, and 25%, respectively. These findings underscore the need for stricter aseptic control in dairy farms to prevent disease transmission between animals and ensure the production of safe and uncontaminated food for human consumption.


Use of an abridged scored Patient-Generated Subjective Global Assessment (abPG-SGA) as a nutritional screening tool for cancer patients in an outpatient setting.
The scored Patient-Generated Subjective Global Assessment tool (PG-SGA), regarded as the most appropriate means of identifying malnutrition in cancer patients, is often challenging to implement in a busy outpatient setting. We assessed the validity of an abridged version of the PG-SGA (abPG-SGA), which forgoes the physical examination, and compared its usefulness in discerning malnutrition to the full PG-SGA and Malnutrition Screening Tool (MST). The nutritional status of 90 oncology outpatients receiving chemotherapy was assessed according to SGA global rating, PG-SGA, and MST. Receiver operating characteristic (ROC) curves were generated to estimate the sensitivity and specificity of various cut-off scores for malnutrition. Thirty-six percent of patients were malnourished (SGA). The abPG-SGA yielded 94% sensitivity and 78% specificity and area under the curve (AUC) = 0.956, which was slightly lower than PG-SGA (97% sensitivity, 86% specificity, AUC = 0.967) and higher than MST (81% sensitivity, 72% specificity, AUC = 0.823). Patient reported symptoms included loss of appetite (30%), altered taste (31%), fatigue (30%), and decreased ability to perform activities of daily living (53%). In conclusion, the abPG-SGA is a practical, informative and valid tool for detecting malnutrition in the outpatient oncology setting.


Long-acting risperidone in stable patients with schizoaffective disorder.
Oral and long-acting risperidone has been shown to be effective for acute and maintenance treatment of patients with schizoaffective disorders. The present analysis investigated the efficacy and tolerability of direct transition from other antipsychotics to risperidone long-acting injectable in patients with schizoaffective disorder. Patients aged > or = 18 years with schizoaffective disorder (DSM-IV), who required a change of medication, received risperidone long-acting injectable 25 mg (increased to 37.5 or 50 mg, if necessary) every 2 weeks for 6 months. The analysis included 249 patients (47% male; mean age 43 years), of whom 74% completed the 6-month study. Mean scores for the total Positive and Negative Syndrome Scale (PANSS) and all three subscales were significantly reduced from baseline to week 4 (p < 0.001), with further improvements until treatment endpoint. Significant improvements from baseline to endpoint were seen in the mood symptom domains of anxiety/depression (10.4+/-4.1 vs 8.7+/-3.9) and uncontrolled hostility/excitement (7.6+/-3.6 vs 6.9+/-3.8). Mean Global Assessment of Function (GAF) score improved significantly from 59.4+/-15.6 at baseline to 66.4+/-17.7 (p < 0.001) at endpoint. Of 87 patients hospitalized at baseline, 67% were discharged at endpoint. Both quality of life (SF-36) and satisfaction with treatment were improved significantly at endpoint. Total ESRS scores fell progressively throughout the study, and the reduction was already statistically significant (p < 0.001) at 4 weeks. Small but statistically significant (p < 0.001) mean shifts of 1.8% were seen in body weight and Body Mass Index (BMI). Patients with schizoaffective disorder derived several benefits from a change to risperidone long-acting injectable, including reductions in psychiatric symptoms (particularly the mood symptom domains) and a reduction in the severity of drug-induced neurological movement disorders.


The ADA in the marketplace.
The Americans With Disabilities Act (ADA) is intended to make employment and treatment of the disabled more fair. It is important for dermatology health care providers to understand and practice several proactive measures to ensure compliance with the ADA.


Activity of commissural interneurons in spinal cord of Xenopus embryos.
Horseradish peroxidase- (HRP) filled microelectrodes have been used to examine the anatomy and physiology of "commissural interneurons," a morphologically defined class of spinal cord interneuron in Xenopus laevis embryos. Commissural interneurons have unipolar cell bodies in the dorsal half of the spinal cord. Their dendrites lie in the mid to ventral parts of the lateral tracts and their axons cross the cord ventrally, T branch, and ascend and descend on the opposite side of the cord. Recordings were made from animals immobilized in tubocurarine and responding to natural stimulation with three patterns of fictive motor activity. During episodes of fictive swimming, commissural interneurons are phasically excited to fire 1 spike/cycle in phase with motor discharge on the same side and receive a midcycle inhibitory postsynaptic potential (IPSP) in phase with motor discharge on the opposite side. Rhythmic activity is superimposed on a background depolarization. During periods of synchrony, phasic excitatory input doubles in frequency so that cells fire with half the swimming cycle period. The background depolarization is generally stronger than during swimming. During periods of fictive struggling, evoked by electrical stimulation of the skin, commissural interneurons fire a burst of spikes per cycle, cells being relatively hyperpolarized when motoneurons on the opposite side are active. In response to ipsilateral skin stimulation, some cells receive an IPSP at a latency of 12-20 ms. This precedes the onset of fictive locomotion. We discuss how anatomy and activity of commissural interneurons is suitable for a reciprocal inhibitory role.


Grain-size analysis of volcanic ash for the rapid assessment of respiratory health hazard.
Volcanic ash has the potential to cause acute and chronic respiratory diseases if the particles are sufficiently fine to enter the respiratory system. Characterization of the grain-size distribution (GSD) of volcanic ash is, therefore, a critical first step in assessing its health hazard. Quantification of health-relevant size fractions is challenging without state-of-the-art technology, such as the laser diffractometer. Here, several methods for GSD characterization for health assessment are considered, the potential for low-cost measurements is investigated and the first database of health-pertinent GSD data is presented for a suite of ash samples from around the world. Methodologies for accurate measurement of the GSD of volcanic ash by laser diffraction are presented by experimental analysis of optimal refractive indices for different magmatic compositions. Techniques for representative sampling of small quantities of ash are also experimentally investigated. GSD results for health-pertinent fractions for a suite of 63 ash samples show that the fraction of respirable (<4 microm) material ranges from 0-17 vol%, with the variation reflecting factors such as the style of the eruption and the distance from the source. A strong correlation between the amount of <4 and <10 microm material is observed for all ash types. This relationship is stable at all distances from the volcano and with all eruption styles and can be applied to volcanic plume and ash fallout models. A weaker relationship between the <4 and <63 microm fractions provides a novel means of estimating the quantity of respirable material from data obtained by sieving.


Results of a Mass Media Campaign in South Africa to Promote a Sugary Drinks Tax.
In South Africa, the increased consumption of sugary drinks has been associated with increased obesity rates. Mass media campaigns can play a crucial role in improving knowledge, shifting attitudes, and building support for government action on reducing sugary drink consumption. No study to date has evaluated the effectiveness of mass media campaigns on the health harms of sugary drinks in South Africa. The purpose of this study was to evaluate the impact of a mass media campaign on knowledge and attitudes around sugary drinks and on public support for a proposed tax on sugary drinks in South Africa. The "Are You Drinking Yourself Sick?" campaign aired in South Africa from October 2016 to June 2017 to shift attitudes toward sugary drinks, build personal risk perceptions of the health harms of consuming sugary drinks, and build public support for a proposed tax on sugary drinks. Campaign impact was measured in representative cross-sectional household surveys of adults ages 18 to 56. The surveys were conducted just prior to the launch of the campaign (N = 1000), from October 7 to 10, 2016, and immediately following its conclusion (N = 1000), from July 12 to 21, 2017. Campaign impact was assessed by comparing changes from the pre-campaign to the post-campaign period on key outcome indicators. In addition, the effect of campaign awareness was analyzed in logistic regression analysis of the post-campaign data. The campaign was recalled by 55% of survey respondents, and 78% of campaign-aware respondents said that the campaign's main message was "drinking sugary drinks can make you sick." There were significant changes from the pre- to the post-campaign period in knowledge that sugary drink consumption can lead to obesity and related health problems and that sugary drinks contribute toward the obesity problem in South Africa. Campaign awareness was also significantly associated with increases in knowledge about the harms of sugary drinks, and in particular, on government action, including the proposed tax on sugary drinks. Media campaigns are an effective intervention for obesity prevention. In addition to improving knowledge and shifting attitudes, media campaigns can effectively build public support for strong government action and therefore must be a component of a comprehensive obesity prevention approach.


Human anterior cingulate cortex neurons encode cognitive and emotional demands.
The cortical mechanisms and substrates of cognitive and emotional demands are poorly understood. Lesion studies and functional imaging implicate the anterior cingulate cortex (ACC). The caudal ACC (cACC) has been implicated in cognitive processes such as attention, salience, interference, and response competition, mostly on the basis of neuroimaging results. To test the hypothesis that individual cACC neurons subserve these functions, we monitored neuronal activity from single cells in the cACC while subjects were engaged in a mental arithmetic task, the cognitively demanding counting Stroop task, and/or the emotional Stroop interference task. We now report the first direct measures of single neurons in humans identifying a population of cACC neurons that respond differentially or in a graded manner to cognitively demanding high- and low-conflict Stroop tasks, including those with emotional valence. These data indicate that cACC neurons may be acting as salience detectors when faced with conflict and difficult or emotional stimuli, consistent with neuroimaging results of cACC responses to abrupt sensory, novel, task-relevant, or painful stimuli.


Effect of dimethyl fumarate on heme oxygenase-1 expression in experimental allergic encephalomyelitis in rats.
Multiple sclerosis (MS) is an autoimmunological disease leading to neurodegeneration. The etiology of the disease remains unknown, which strongly impedes the development of effective therapy. Most MS treatments focus on modulating the activity of the immune system. Dimethyl fumarate (DMF) exerts a broad spectrum of action, such as modulating immune cell differentiation towards anti-inflammatory subtypes, influencing cytokine production, regulating immune cell migration into the central nervous system, and activating intracellular antioxidant mechanisms. It is well established that activation of the nuclear factor E2 (Nrf2)-dependent pathway, leading to expression of the second-phase antioxidant enzymes, is influenced by DMF. In our experiments we used female Lewis rats in an animal model of MS - experimental allergic encephalomyelitis (EAE). The rats were fed with dimethyl fumarate to test the expression of heme oxygenase-1 (HO-1), one of the second-phase antioxidant enzymes, at specific time points of the symptomatic phases of the disease: on the first day of the occurrence of clinical symptoms (10th day post immunization, DPI); at the peak of clinical symptoms (14th DPI); and at the end of the relapse (21st DPI). The results showed that HO-1 expression, at both the mRNA and protein level, is influenced by DMF administration only at the very beginning of the symptomatic phase of EAE, and not at the peak of clinical symptoms, nor at the end of the relapse. This indicates that the regulation of the Nrf2-dependent antioxidant pathway by DMF occurs at a certain time interval (early EAE/MS) and strongly underlines the importance of the earliest introduction of the therapy to the patient. .


[A case of intrasacular thrombosis during the coil embolization procedure for a ruptured cerebral aneurysm].
A case of intrasacular thrombosis during the coil embolization procedure for a ruptured cerebral aneurysm is presented. A 50-year-old man suffered sudden onset of headache and unconsciousness. Computed tomography demonstrated diffuse subarachnoid hemorrhage and magnetic resonance angiography (MRA) disclosed a basilar-right superior cerebellar artery aneurysm. The aneurysm was treated by endovascular coil embolization with Guglielmi detachable coil (GDC; Boston Scientific Corp., Natick, MA, USA). The diameter of the aneurysm sac was 3.7 mm X 2.7 mm at first, but during the coil delivery the aneurysm size was diminished by thrombosis in the sac. GDC-10 2 mm X 2 cm was able to be placed in the aneurysm successfully after additonal administration of heparin, and postembolization angiography revealed obliteration of the aneurysm. Fortunately, there was no ischemic complication and the patient was discharged without any neurological deficits. MRA study 7 months after treatment revealed no recurrence of the aneursym, but long-term follow-up will be needed because of the low packing density in the aneurysm. Thromboembolic complication is one of the main complications of aneurysm coil placement for ruptured both cerebral aneurysms, and unruptured cerebral aneurysms. The administration of anticoagulant and antiplatelet agents is necessary during coil embolization for ruptured cerebral aneurysms.


Identification of a Metastasis-Related Protein IFI16 in Esophageal Cancer using a Proteomic Approach.
Background: Metastasis is the leading cause of the high morality of esophageal squamous cell carcinoma (ESCC), so early monitoring metastasis of esophageal cancer is the key to improve the survival rate of ESCC patients. However, there have not been effective biomarkers for predicting metastasis of ESCC patients,it is an urgent need to identify ESCC metastasis-related proteins. Methods: iTRAQ-based proteomic method was performed in highly metastatic 30M cell established in our previous study and the corresponding parental cells KYSE30.The expression of IFI16 was verified using western blotting and immunohistochemistry (IHC). Then, cck8, transwell assay,mouse metastasis experiments were performed to determine the functional role of IFI16 in esophageal cancer. Finally, RAN-Seq, qpcr, transwell assay were used to investigate the underlying mechanism of IFI16 in esophageal cancer metastasis. Results: The data showed that IFI16 was upregulated in 30M cell compared with KYSE30 cell. IFI16 also increased in ESCC tumor compared with non-tumor tissue. Kaplan-Meier survival curve analysis showed that the relapse-free survival (RFS) of patients with high IFI16 level was worse than that of patients with low IFI16 level (P=0.0449). In addition, IFI16 knockdown did not affect the cell growth, but inhibited ESCC cell migration and invasion in ESCC cells. Moreover, IFI16 knockdown suppressed the lung metastasis of 30M cells in mouse models. Finally, we performed an RNA-Seq assay in IFI16-knocking down 30M cells and identified that knocking down IFI16 downregulated the expression of fibroblast growth factor proteins (FGF1, FGF2 etc.). Furthermore, overexpressing FGF1 and FGF2 rescued the lost of migration and invasion ability of 30M mediated by IFI16 knockdown. Conclusion: Our results demonstrated that IFI16 was a key ESCC metastasis-related protein and played a role in ESCC metastasis through promoting the FGF proteins expression.


Anatomy of Abelian and non-Abelian fractional quantum Hall states.
We deduce a new set of symmetries and relations between the coefficients of the expansion of Abelian and non-Abelian fractional quantum Hall (FQH) states in free (bosonic or fermionic) many-body states. Our rules allow us to build an approximation of a FQH model state with an overlap increasing with growing system size (that may sometimes reach unity) while using a fraction of the original Hilbert space. We prove these symmetries by deriving a previously unknown recursion formula for all the coefficients of the Slater expansion of the Laughlin, Read-Rezayi, and many other states (all Jacks multiplied by Vandermonde determinants), which completely removes the current need for diagonalization procedures for these model Hamiltonians.


Amino-terminal pro-brain natriuretic peptide: a biomarker for diagnosis, prognosis and management of heart failure.
There is a substantial need for a diagnostic tool to aid in the early diagnosis of heart failure and in the recognition of those at risk for its development, as well as in guidance of therapy. Testing for amino-terminal pro-brain natriuretic peptide (NT-proBNP) has been recognized to have utility in the diagnosis, prognosis and management of heart failure. In addition, numerous other applications for NT-proBNP testing are now recognized, such as evaluation of patients with heart disease in the absence of heart failure, as well as the diagnostic and prognostic evaluation of patients with acute coronary syndromes or pulmonary thromboembolism.


Force autocorrelation function in linear response theory and the origin of friction.
Vanishing of the equilibrium fluctuation expression for the friction coefficient of a massive particle in a finite-volume liquid has been well documented and discussed in literature. This paper investigates the decay of the friction force in the corresponding nonequilibrium situation, when the massive particle moves through a finite volume at a constant velocity. The friction force ultimately vanishes (with the decay form as predicted by the equilibrium integral) because of the finite mass of the rest of the system, which allows it to be dragged by the moving particle. However, it is sufficient to have two infinite masses moving relative to each other in a finite liquid volume for the friction force to be finite at all times.


A Physician's Attempt to Self-Medicate Bipolar Depression with N,N-Dimethyltryptamine (DMT).
N,N-dimethyltryptamine (DMT) is a psychoactive substance that has been gaining popularity in therapeutic and recreational use. This is a case of a physician who chronically took DMT augmented with phenelzine in an attempt to self-medicate refractory bipolar depression. His presentation of altered mental status, mania, and psychosis is examined in regards to his DMT use. This case discusses DMT, the possible uses of DMT, and the theorized mechanism of DMT in psychosis and treatment of depression, particularly involving its agonist activity at 5-HT1A, 5-HT2A, and 5-HT2C. It is also important to recognize the dangers of self-medication, particularly amongst physicians.


Cullin7 induces docetaxel resistance by regulating the protein level of the antiapoptotic protein Survivin in lung adenocarcinoma cells.
Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer (NSCLC). Chemotherapy resistance is the main cause of chemotherapy failure. Cullin7 (Cul7) is highly expressed in LUAD and is associated with poor prognosis. Moreover, Cul7 is abnormally overexpressed in docetaxel-resistant LUAD cells. Therefore, further exploration of the role and molecular mechanism of Cul7 in LUAD docetaxel resistance is necessary. We established docetaxel-resistant cell lines (A549DTX and H358DTX cell lines) by exposing cells to gradually increasing concentrations of docetaxel. Cell (A549, A549DTX, H358, and H358DTX cell lines) sensitivity to docetaxel was determined via a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymmethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. And then quantitative polymerase chain reaction (qPCR) and Western blotting were performed to measure the expression of Cul7 and Survivin in A549, A549DTX, H358, and H358DTX cell lines. Subsequently, we knocked down Cul7 in docetaxel-resistant cells and overexpressed Cul7 in parental cells via lentiviral transduction to further validate the correlation between Cul7 and docetaxel resistance, while exploring the molecular mechanism of docetaxel resistance it caused. Immunofluorescence and immunohistochemical (IHC) staining were also used to evaluate the expression and cellular localization of Cul7. To confirm the effect of Cul7 expression on cell apoptosis, we used flow cytometry to detect the apoptosis rate of A549 and A549DTX cells with the same drug concentration. Cul7 was highly expressed in A549DTX and H358DTX cells. However, when Cul7 expression was knocked down in A549DTX and H358DTX cells, cell sensitivity to docetaxel was significantly increased. In addition, we found that Cul7 was coexpressed with Survivin. Silencing Survivin reversed the docetaxel insensitivity caused by Cul7 overexpression. High expression of Cul7 and Survivin in docetaxel-resistant LUAD cells inhibited the intrinsic apoptosis pathway and promoted cell proliferation. Therefore, the Cul7/Survivin axis may play a role in inducing LUAD docetaxel chemoresistance. Cul7 and Survivin were both highly expressed in docetaxel-resistant LUAD cells. Our results suggest that Cul7 may inhibit apoptosis and promote the proliferation of LUAD cells by increasing the Survivin protein level, which in turn contributes to docetaxel chemoresistance in LUAD.


Fermentation of red ginseng extract by the probiotic Lactobacillus plantarum KCCM 11613P: ginsenoside conversion and antioxidant effects.
Ginsenosides, which are bioactive components in ginseng, can be converted to smaller compounds for improvement of their pharmacological activities. The conversion methods include heating; acid, alkali, and enzymatic treatment; and microbial conversion. The aim of this study was to determine the bioconversion of ginsenosides in fermented red ginseng extract (FRGE). Red ginseng extract (RGE) was fermented using Lactobacillus plantarum KCCM 11613P. This study investigated the ginsenosides and their antioxidant capacity in FRGE using diverse methods. Properties of RGE were changed upon fermentation. Fermentation reduced the pH value, but increased the titratable acidity and viable cell counts of lactic acid bacteria. L. plantarum KCCM 11613P converted ginsenosides Rb2 and Rb3 to ginsenoside Rd in RGE. Fermentation also enhanced the antioxidant effects of RGE. FRGE reduced 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity and reducing power; however, it improved the inhibition of β-carotene and linoleic acid oxidation and the lipid peroxidation. This suggested that the fermentation of RGE is effective for producing ginsenoside Rd as precursor of ginsenoside compound K and inhibition of lipid oxidation. This study showed that RGE fermented by L. plantarum KCCM 11613P may contribute to the development of functional food materials.


Cre-ativity in the liver: transgenic approaches to targeting hepatic nonparenchymal cells.
Rapid evolution in transgenic (Tg) mouse technology now permits cell-specific and temporal control of fluorescent cell-labeling and gene inactivation. Here, we discuss the principal strategies that have been utilized to target, label, and manipulate hepatic nonparenchymal cells, with emphasis on the utility of constitutive and inducible Cre-lox systems. We summarize key findings of studies employing Tg technology to target hepatic stellate cells, myofibroblasts, liver sinusoidal endothelial cells, and macrophages to illustrate the power of these approaches in identifying cell-specific molecular mechanisms critical to the pathophysiology of liver disease. Increasing adoption of Tg techniques will help to answer fundamental questions regarding the pathogenesis of hepatic diseases and provide the mechanistic rationale to allow identification of novel drug targets, ultimately translating into effective therapies for patients with liver disease.


An antibody toolkit for the study of membrane traffic in Drosophila melanogaster.
The use of Drosophila melanogaster as a model organism has been pivotal to understanding the developmental processes of metazoans. However, the use of flies for studying subcellular organization is hampered by a paucity of reliable reagents to label specific organelles. Here, we describe the generation of mouse monoclonal antibodies against a set of markers of the secretory and endocytic pathways, along with goat polyclonal antibodies against two Golgi proteins. We show that the monoclonal antibodies are highly specific and sufficiently sensitive to detect endogenous proteins in crude extracts by immunoblotting with little background staining. By immunofluorescence the major compartments of the membrane traffic system (including the endoplasmic reticulum, the Golgi, and early and late endosomes) are labeled by at least one antibody. Moreover, the antibodies can be used to label organelles in fly tissues including salivary glands and wing imaginal discs. We anticipate that these antibodies will provide a useful tool kit to facilitate the investigation of how the endomembrane system functions and varies in the diverse tissue types of metazoans.


A randomized trial of labor analgesia in women with pregnancy-induced hypertension.
The purpose of this study was to compare the peripartum and perinatal effects of epidural with intravenous labor analgesia in women with pregnancy-induced hypertension. Women with pregnancy-induced hypertension who had consented to participate were randomized to receive either epidural or intravenous analgesia for labor pain. Both methods were given according to standardized protocols. All women received magnesium sulfate seizure prophylaxis. Obstetric and neonatal outcomes were compared according to intent-to-treat allocation. Seven hundred thirty-eight women were randomized: 372 women were given epidural analgesia, and 366 women were given intravenous analgesia. Maternal characteristics were similar, including the severity of hypertension. Epidural analgesia was associated with a significantly prolonged second-stage labor, an increase in forceps deliveries, and an increase in chorioamnionitis. Cesarean delivery rates and neonatal outcomes were similar. Pain relief was superior with the epidural method. Hypotension required treatment in 11% of women in the epidural group. Epidural labor analgesia provides superior pain relief but no additional therapeutic benefit to women with pregnancy-induced hypertension.


Longitudinal clinical studies with antimicrobial mouthrinses.
This chapter examines the use of long-term clinical studies to evaluate the effectiveness of antimicrobial mouthrinses in the prevention and/or treatment of plaque and gingivitis. Such studies should be double-blind, compare the active agent to a control, and last a minimum of 6 months. Such a time interval simulates a common recall interval, enables one to utilize a thorough dental prophylaxis at the initiation of the study, and is sufficient time to observe the development of toxic and other side-effects of therapy. The microbiological component should estimate plaque quantitatively and demonstrate that no pathogenic, opportunistic or resistant micro organisms develop. The indices and microbiology should be performed at baseline, and intermediate period and at 6 months. Thus far, published studies meeting these criteria support the efficacy of listerine and chlorhexidine as agents useful in reducing plaque and gingivitis. Preliminary evidence indicates that sanguinarine may also be effective. The most common side effect of listerine was the complaint of poor taste. Increased stain and calculus formation were cited as the most significant side-effects of chlorhexidine. Such side-effects must be taken into consideration when recommending effective antimicrobial mouthrinses for patient use.


Diagnostic Accuracy of MRI in Knee Meniscus Tear and ACL Injury.
Knee injuries are very common and may lead to other secondary injuries if effective treatment is lacking. In addition to standardized physical examination, magnetic resonance imaging (MRI) is sometimes considered an aid in the diagnosis of knee trauma. In order to have a more accurate diagnosis of knee injuries, we compared MRI with arthroscopic findings in this study to evaluate the diagnostic accuracy of MRI for meniscal tears and anterior cruciate ligament injuries of the knee. One hundred and ten patients with suspected meniscal tears and anterior cruciate ligament injuries of the knee who were admitted to our hospital from June 2020 to June 2022 were selected as study subjects, and the clinical data of the patients were retrospectively analyzed. All patients underwent MRI for preoperative diagnosis, and the sensitivity, specificity, MRI findings, and confirmation of diagnosis were compared and analyzed, and the accuracy of MRI in diagnosing meniscal tears and ACL injuries of the knee was analyzed. The mean ACL angle was (98.0 ± 5.4) in the MRI group and (118.0 ± 6.8) in the arthroscopic group, the difference between the two groups was statistically significant P < .05. The mean L/H value of the ACL was (2.12 ± 0.38) in the MRI group and (1.81 ± 0.19) in the arthroscopic group, which was statistically different between the two groups (P < .05). Among the patients, 68 meniscal injuries were found in the MRI examination, including 45 cases of knee meniscal tears and 23 cases of anterior cruciate ligament injuries. The sensitivity, specificity, positive and negative predictive values, agreement rate, kappa value, and Youden index of MRI in diagnosing meniscal tears and ACL injuries were all high. In terms of sensitivity and accuracy, MRI is an excellent imaging technique for the diagnosis of meniscal tears and anterior cruciate ligament injuries of the knee.


Hemodynamic and arrhythmogenic effects of aconitine applied to the left atria of anesthetized cats. Effects of amiodarone and atropine.
The arrhythmogenic and hemodynamic effects of 0.04% aconitine solution applied locally to the left atria of cats and the effects of amiodarone (10 mg/kg) and atropine (0.2 mg/kg) on the responses to aconitine were investigated. Cats were anesthetized with sodium pentobarbital. The left atrial and limb lead electrocardiograms and the arterial pressure were recorded. Cardiac output was determined with the thermo dilution technique. Aconitine nitrate induced dysrhythmias lasting for a mean of 111 min. Atrial fibrillation occurred in 47% of the animals. A long-lasting (at least 3 hr) cardiodepressant action was seen in response to aconitine. Pretreatment with atropine largely prevented the hemodynamic effects of aconitine and prevented fibrillation. However, mean maximum atrial rates recorded during successive 5 min intervals were similar in control and atropine-treated animals. Amiodarone suppressed dysrhythmias in both atropine-treated and nontreated animals at a dose which exerted only minimal cardiodepression. The method described for evaluating potential activity against supraventricular dysrhythmias in the cat is relatively simple, reproducible, and suitable for statistical analyses. Aconitine appears to exert a long-lasting cholinergic action which may be involved in the genesis of aconitine-induced atrial fibrillation.


Rehabilitation and education are underutilized for mild stroke and TIA sufferers.
Transient ischemic attack (TIA) and mild stroke represent a large proportion of cerebrovascular events, at high risk of being followed by recurrent, serious events. The importance of early education addressing risk management, secondary prevention and lifestyle modifications is the centerpiece of further stroke prevention. However, delivering education and rehabilitation to this population can be complex and challenging. Via synthesis of a narrative review and clinical experience, we explore the unique and inherent complexities of rehabilitation management and education provision for patients following mild stroke and TIA. A considerable proportion of TIA/mild stroke survivors have ongoing rehabilitation needs that are poorly addressed. The need for rehabilitation in these patients is often overlooked, and available assessment tools lack the sensitivity to identify common subtle impairments in cognition, mood, language and fatigue. Active and accessible education interventions need to be initiated early after the event, and integrated with ongoing rehabilitation management. Priority areas in need of future development in this field are highlighted and discussed. Implications for rehabilitation Survivors of mild stroke and TIA have ongoing unmet rehabilitation needs and require a unique approach to rehabilitation and education. Rehabilitation needs are difficult to assess and poorly addressed in this cohort, where available assessment tools lack the sensitivity required to identify subtle impairments. Education needs to be initiated early after the event and involve active engagement of the patient in order to improve stroke knowledge, mood and motivate adherence to lifestyle modifications and secondary prevention. Rehabilitation physicians are currently an underutilized resource, who should be more involved in the management of all patients following TIA or mild stroke.


Changes to the object recognition system in patients with dementia of the Alzheimer's type.
Do DAT patients show category-specific deficits in object identification, and do they arise from semantic or visual damage? Participants decided whether line drawings of living and nonliving objects matched names at superordinate, basic, or subordinate levels. Patients were most impaired with superordinate decisions. Controls had most difficulty with subordinate decisions. No category-specific deficit was found with patients. Impaired superordinate decisions by the patients support semantic damage. If category-specific deficits arise from damaged semantics, they should have been found. Since they were not, and since patients performed subordinate decisions the best, a visual basis to category specificity is supported. Finally, a living advantage was found with normal observers which cannot be spurious due to differences in concept familiarity since living and nonliving objects were matched for this variable.


Activation of PPARγ at an Early Stage of Differentiation Enhances Adipocyte Differentiation of MEFs Derived from Type II Diabetic TSOD Mice and Alters Lipid Droplet Morphology.
Type 2 diabetic Tsumura, Suzuki, obese, diabetes (TSOD) mice gradually gain weight as compared to corresponding Tsumura, Suzuki, non-obesity (TSNO) control mice, and develop insulin resistance. Although development of type 2 diabetes mellitus is associated with dysfunction of adipocytes, little is known about the properties of adipocytes from TSOD mice. Therefore, we attempted to remove intracorporeal factors and elucidate inherent properties of adipocytes of TSOD mice using adipocytes differentiated from mouse embryonic fibroblasts (MEFs) in vitro. Here, we show that MEFs of TSOD have low potency for differentiation into adipocytes. The percentage of Oil red O-stained cells and levels of adipogenic markers in cells differentiated from MEFs of TSOD are lower than those in cells differentiated from MEFs of TSNO. We further show that treatment with an agonist of peroxisome proliferator-activated receptor-γ (PPARγ) (rosiglitazone) at an early stage of differentiation increases the percentage of Oil red O-stained cells in TSOD-MEFs differentiated into adipocytes. Moreover, the lipid droplet size in those adipocytes is larger than that in the adipocytes differentiated from MEFs of TSNO. Although persistent treatment of MEFs of TSOD with rosiglitazone during differentiation increases the percentage of Oil red O-stained cells, the lipid droplet size in adipocytes treated as such does not reach the size of those treated in early stage only. Thus, activation of PPARγ by its agonist at an early stage of differentiation compensates for the low potency toward adipogenic differentiation of, and accelerates formation of enlarged lipid droplets in adipocytes derived from, MEFs of TSOD mice.


The microRNA repertoire of Tibetan naked carp Gymnocypris przewalskii: A case study in Schizothoracinae fish on the Tibetan Plateau.
Tibetan naked carp Gymnocypris przewalskii is an ideal model system to study highland adaptation of fish, because it evolved specific genetic and phenotypic characteristics to adapt to chronic cold and alkaline environments in Lake Qinghai. MicroRNAs (miRNAs) are small noncoding RNAs that regulating gene expression post-transcriptionally in a wide range of biological processes. In this study, we focus on the role of miRNAs in adaptation of G. przewalskii to extreme conditions in Lake Qinghai. We generate the first miRNAome of G. przewalskii in Schizothoracinae fish. Using several genomic resources, we inferred 341 conserved miRNAs belonged to 152 miRNA families and 43 novel miRNAs in G. przewalskii, and also identified 15 teleost-specific miRNAs. Using a large scale of conserved miRNAs, we constructed a high-confidence phylogenetic tree between teleost and mammals than mitochondria and nuclear genes. In addition, we found that several miRNA family (e.g. miR-10 and let-7) members highly expressed in G. przewalskii, which may function in multiple biological processes. Finally, we predicted a total of 34,258 miRNA targets genes. Conserved miRNAs target genes participating in signal transduction, cell differentiation and biosynthetic process, and showed signature of functional constraint. While novel miRNAs in a species displayed species-specific targets and involved in ion binding, transport and oxidoreductase activity, may affect the expression patterns of targets with signature of gene family expansion or positive selection under extreme environment. Taken together, this study demonstrated that miRNAs may involve into roles of adaptation of G. przewalskii to highland aquatic environment, and also provide insights into miRNA regulatory network in Schizothoracinae fish as a case study.


[Generation of a series of recombinant herpes simplex viruses which can provide replicating and packaging functions for recombinant adeno-associated virus].
To construct a series of recombinant herpes simplex viruses that can provide replicating and packaging functions for recombinant adeno-associated virus (rAAV), and to select the strains possessing stronger functions for large-scale production of rAAV. A set of cosmids that represents the whole genome of HSV-1 was used to generate recombinant HSV-1 expressing rep and cap proteins of AAV-2. An ATG-to-ACG mutation in the start codon of AAV-2 rep protein was generated by site-directed mutagenesis. rep and cap genes, under control of their native promoters, with or without the ATG-to-ACG mutation in the start codon of rep, were inserted into the Xba site of UL2 or UL44 genes, respectively, resulting in the recombinant cosmids cos6-rmc/ UL2, cos56-rc/ UL44 and cos56-rmc/ UL44. Homologous recombination among the HSV-1 fragment on the recombinant cosmids and the rest fragments of HSV-1 genome resulted in three strains of recombinant HSV-1. Together with the one was constructed previously, there were four strains of recombinant HSV-1named HSV1-rc/ UL2, HSV1-rmc/ UL2, HSV1-rc/ UL44 and HSV1-rmc/ UL44 respectively. PCR detection confirmed the existence of rep- gene in the genomes of all four strains of the recombinant HSV-1. Recombinant AAV was produced after infecting the AAV vector cell line that carrying the GFP expression cassette with the four strains of recombinant HSV-1 respectively. However, HSV1-rc/ UL2 and HSV1-rmc/ UL2 produced much more rAAV than HSV1-rc/ UL44 and HSV1c/ UL44 did. All the four strains of recombinant HSV-1 support rAAV replication and packaging. HSV1 UL2 and HSV1-rmc/ UL2 that provide much stronger functions may be useful for large-scale production of rAAV.


The Comparison of the Protective Effects of α- and β-Antithrombin against Vascular Endothelial Cell Damage Induced by Histone in Vitro.
Antithrombin is a promising option for the treatment of sepsis, and vascular endothelium is an important target for this fatal condition. Here, we aimed to evaluate the protective effects of different glycoforms of antithrombin on histone-induced endothelial cell damage and explore the responsible mechanisms in an experimental model in vitro. Endothelial cells were treated in vitro using histone H4 to induce cellular damage. Various doses of either α- or β-antithrombin were used as treatment interventions, and both cell viability and the levels of lactate dehydrogenase (LDH) in the medium were assessed. Endothelial cell damage was also assessed using microscopic examination and immunofluorescent staining with anti-syndecan-4 and anti-antithrombin antibodies. As a result, both glycoforms of antithrombin significantly improved cell viability when administered at a physiological dose (150 μg/mL). Cellular injury as evaluated using the LDH level was significantly suppressed by β-antithrombin at a supranormal dose (600 μg/mL). Microscopic observation suggested that β-antithrombin suppressed the endothelial cell damage more efficiently than α-antithrombin. β-Antithrombin suppressed the intensity of syndecan-4 staining which became evident after treatment with histone H4, more prominently than α-antithrombin. The distribution of antithrombin was identical to that of syndecan-4. In conclusion, both α- and β-antithrombin can protect vascular endothelial cells from histone H4-induced damage, although the effect was stronger for β-antithrombin. The responsible mechanisms might involve the binding of antithrombin to the glycocalyx on the endothelial surface. These results provide a theoretical basis for the application of antithrombin to the prevention and treatment of sepsis-related endothelial damage.


Quantification and minimization of uncertainties of internal target volume for stereotactic body radiation therapy of lung cancer.
To quantify uncertainties in delineating an internal target volume (ITV) and to understand how these uncertainties may be individually minimized for stereotactic body radiation therapy (SBRT) of early stage non-small cell lung cancer (NSCLC). Twenty patients with NSCLC who were undergoing SBRT were imaged with free-breathing 3-dimensional computed tomography (3DCT) and 10-phase 4-dimensional CT (4DCT) for delineating gross tumor volume (GTV)(3D) and ITV(10Phase) (ITV3). The maximum intensity projection (MIP) CT was also calculated from 10-phase 4DCT for contouring ITV(MIP) (ITV1). Then, ITV(COMB) (ITV2), ITV(10Phase+GTV3D) (ITV4), and ITV(10Phase+ITVCOMB) (ITV5) were generated by combining ITV(MIP) and GTV(3D), ITV(10phase) and GTV(3D), and ITV(10phase) and ITV(COMB), respectively. All 6 volumes (GTV(3D) and ITV1 to ITV5) were delineated in the same lung window by the same radiation oncologist. The percentage of volume difference (PVD) between any 2 different volumes was determined and was correlated to effective tumor diameter (ETD), tumor motion ranges, R(3D), and the amplitude variability of the recorded breathing signal (v) to assess their volume variations. The mean (range) tumor motion (R(SI), R(AP), R(ML), and R(3D)) and breathing variability (v) were 7.6 mm (2-18 mm), 4.0 mm (2-8 mm), 3.3 mm (0-7.5 mm), 9.9 mm (4.1-18.7 mm), and 0.17 (0.07-0.37), respectively. The trend of volume variation was GTV(3D) <ITV1 <ITV2 ≈ ITV3 < ITV4 < ITV5. The means ± SDs of these volumes were 11.1 ± 9.3 cc, 13.2 ± 10.5 cc, 14.9 ± 11.0 cc, 14.7 ± 11.4 cc, 15.9 ± 11.7 cc, and 16.4 ± 11.8 cc, respectively. All comparisons between the target volumes showed statistical significance (P≤.001), except for ITV2 and ITV3 (P=.594). The PVDs for all volume pairs correlated negatively with ETD (r≤-0.658, P≤.006) and positively with R(3D) (r≥0.503, P≤.047). The PVDs for pairs of ITV2 vs ITV5 and ITV5 vs ITV4 negatively correlated with ETD (r=0.502, -0.626; P=.047, .010). No other correlation was found. Uncertainties in individualized ITVs for SBRT of early stage NSCLC could effectively be minimized by combining information from 3DCT, 4DCT, and MIP. If these images cannot be efficiently contoured, a combination of ITV(MIP) and GTV(3D) could be an effective alternative.


Infantile Cocktail of Erythropoietin and Melatonin Restores Gait in Adult Rats with Preterm Brain Injury.
Cerebral palsy (CP) is the most common cause of physical disability for children worldwide. Many infants and toddlers are not diagnosed with CP until they fail to achieve obvious motor milestones. Currently, there are no effective pharmacologic interventions available for infants and toddlers to substantially improve their trajectory of neurodevelopment. Because children with CP from preterm birth also exhibit a sustained immune system hyper-reactivity, we hypothesized that neuro-immunomodulation with a regimen of repurposed endogenous neurorestorative medications, erythropoietin (EPO) and melatonin (MLT), could improve this trajectory. Thus, we administered EPO + MLT to rats with CP during human infant-toddler equivalency to determine whether we could influence gait patterns in mature animals. After a prenatal injury on embryonic day 18 (E18) that mimics chorioamnionitis at ∼25 weeks human gestation, rat pups were born and raised with their dam. Beginning on postnatal day 15 (P15), equivalent to human infant ∼1 year, rats were randomized to receive either a regimen of EPO + MLT or vehicle (sterile saline) through P20. Gait was assessed in young adult rats at P30 using computerized digital gait analyses including videography on a treadmill. Results indicate that gait metrics of young adult rats treated with an infantile cocktail of EPO + MLT were restored compared to vehicle-treated rats (p < 0.05) and similar to sham controls. These results provide reassuring evidence that pharmacological interventions may be beneficial to infants and toddlers who are diagnosed with CP well after the traditional neonatal window of intervention.


Insular epilepsy masquerading as multifocal cortical epilepsy as proven by depth electrode.
The insular cortex is an uncommon epileptogenic location from which complex partial seizures may arise. Seizure activity in insular epilepsy may mimic temporal, parietal, or other cortical areas. Semiology, electroencephalography, and even surface electrocorticography recordings may falsely localize other cortical foci, leading to inaccurate diagnosis and treatment. The use of insular depth electrodes allows more precise localization of seizure foci. The authors describe the case of a young girl with seizures falsely localized to the cortex, with foci arising from the insula, as proven by depth electrode recordings. Resection of the insula yielded seizure control.