Medical Student Experiences on Consultation-Liaison Psychiatry Rotations: A Nationwide Survey.
Consultation-liaison (C-L) psychiatry clerkship rotations may improve medical students' understanding of psychiatric principles relevant to the settings in which they will ultimately practice. This study aimed to characterize students' experiences on C-L rotations. This cross-sectional survey study, sponsored by the Academy of Psychosomatic Medicine Subcommittee on Medical Student Education, was conducted at 5 US medical schools between 2012 and 2016. After the C-L rotation, students completed a voluntary 17-item survey. A total of 235 surveys were collected (mean response rate = 92%). The most frequently endorsed benefit of C-L was learning to manage psychiatric disorders in the context of medical illness (89%). The most frequently endorsed drawback was inconsistent/excessively variable workload (40%). Overall, 82% of respondents recommended C-L to other students; 80% reported that the ideal clerkship would include exposure to both C-L and inpatient psychiatry. Overall, 38% reported that their C-L experience increased their interest in psychiatry as a career. Effect of C-L on interest in psychiatry did not differ by study site, age, sex, clerkship length, or time spent on C-L. Respondents who noted more positive role-modeling on C-L compared to other clerkship rotations were more likely to report increased interest in a psychiatry career (odds ratio = 2.70). Most medical students perceive C-L rotations favorably. Positive role modeling may increase their consideration of psychiatry specialization. The findings that C-L rotation length did not correlate with attitudes and that most students preferred exposure to both inpatient and C-L psychiatry suggest that C-L exposure can beneficially be integrated into core clerkships containing other elements.


Psilocybin modulation of time-varying functional connectivity is associated with plasma psilocin and subjective effects.
Psilocin, the neuroactive metabolite of psilocybin, is a serotonergic psychedelic that induces an acute altered state of consciousness, evokes lasting changes in mood and personality in healthy individuals, and has potential as an antidepressant treatment. Examining the acute effects of psilocin on resting-state time-varying functional connectivity implicates network-level connectivity motifs that may underlie acute and lasting behavioral and clinical effects. Evaluate the association between resting-state time-varying functional connectivity (tvFC) characteristics and plasma psilocin level (PPL) and subjective drug intensity (SDI) before and right after intake of a psychedelic dose of psilocybin in healthy humans. Fifteen healthy individuals completed the study. Before and at multiple time points after psilocybin intake, we acquired 10-minute resting-state blood-oxygen-level-dependent functional magnetic resonance imaging scans. Leading Eigenvector Dynamics Analysis (LEiDA) and diametrical clustering were applied to estimate discrete, sequentially active brain states. We evaluated associations between the fractional occurrence of brain states during a scan session and PPL and SDI using linear mixed-effects models. We examined associations between brain state dwell time and PPL and SDI using frailty Cox proportional hazards survival analysis. Fractional occurrences for two brain states characterized by lateral frontoparietal and medial fronto-parietal-cingulate coherence were statistically significantly negatively associated with PPL and SDI. Dwell time for these brain states was negatively associated with SDI and, to a lesser extent, PPL. Conversely, fractional occurrence and dwell time of a fully connected brain state partly associated with motion was positively associated with PPL and SDI. Our findings suggest that the acute perceptual psychedelic effects induced by psilocybin may stem from drug-level associated decreases in the occurrence and duration of lateral and medial frontoparietal connectivity motifs. We apply and argue for a modified approach to modeling eigenvectors produced by LEiDA that more fully acknowledges their underlying structure. Together these findings contribute to a more comprehensive neurobiological framework underlying acute effects of serotonergic psychedelics.


[Qualitative and quantitative methods of betulonic acid in fruits of Liquidambar formosana].
To develop the identification and assay methods for betulonic acid in fruits of Liquidambar formosana. TLC method was used for identification with silica gel G plate and petroleum ether(60-90 degrees C)-acetone (17:3) as a developing solvent. Betulonic acid in ethanol extract was separated on the ODS column with methanol-water-glacial acetic acid (87:13:0.1) as mobile phase. Flow-rate was 1.0 mL x min(-1), and column temperature 35 degrees C. ELSD drift-tube temperature was 82 degrees C, and gas flow 1.25 L x min(-1). The qualitative method is repeatable. Betulonic acid in ethanol extracts is well separated, relationship of logarithms of injection amount and peak area is linear (r = 0.9997) within the range of 0.65-3.25 microg. The average recovery is 98.0% and RSD of repeatability is 2.5%. 11 crude drugs purchased from different areas in the country were identified and quantified with the methods. The methods and data could be used for quality control of fruits of L. formosana.


Cell death induced by flavonoid glycosides with and without copper.
The ability of flavonoid glycosides isolated from several plants to induce DNA breakage was examined using supercoiled plasmid pBR322 DNA by agarose gel electrophoresis in the presence of Cu(II). Among all the compounds, 1, 4, and 6 could cause significant breakages of supercoiled plasmid pBR322 DNA in the presence of Cu(II). Cu(I) was not shown to be an essential intermediate in the process of pBR322 DNA breakage by using the Cu(I)-specific sequestering reagent neocuproine. A decreased cell viability was enhanced in gastric carcinoma SCM-1 cells treating with lower concentrations of 1 and 6 when cotreated with increased concentrations of Cu(II), respectively. Treatments of SCM-1 cells with 500 microM of 1 in the presence of 300 or 500 microM of Cu(II) inhibited the Cu(II)-induced apoptosis. Compound 1 (500 microM) could prevent cell death by inhibiting the 500 microM Cu(II)-induced apoptosis and necrosis, but did not have any effect on the mitochondrial membrane potential changed by 500 microM Cu(II). Both compounds 1 and 6 could inhibit the DNA breakages caused by O2- while 1 also revealed inhibitory effect on xanthine oxidase with an IC50 value of 22.7+/-6.9 microM. These results indicated that compound 1 with a higher concentration may probably mediate through the suppression of xanthine oxidase activity and reduce reactive oxygen species (ROS) induced by high concentration of Cu(II) (500 microM) and prevent the following cell death.


Uterine diseases in cattle after parturition.
Bacterial contamination of the uterine lumen is common in cattle after parturition, often leading to infection and uterine disease. Clinical disease can be diagnosed and scored by examination of the vaginal mucus, which reflects the presence of pathogenic bacteria such as Escherichia coli and Arcanobacterium pyogenes. Viruses may also cause uterine disease and bovine herpesvirus 4 (BoHV-4) is tropic for endometrial cells, causing a rapid cytopathic effect. The elimination of pathogens by the innate immune system is dependent on pattern recognition receptors binding pathogen-associated molecules. Uterine epithelial and stromal cells express receptors such as Toll-like Receptor 4 that binds E. coli lipopolysaccharide. The infertility associated with uterine disease is caused by damage to the endometrium and disruption of ovarian cyclic activity. Bacteria modulate endometrial prostaglandin secretion, and perturb ovarian follicle growth and function. Understanding the molecular basis of uterine disease will lead to novel approaches to treating infertility.


The effect of diaminoalkyl-anthraquinone derivatives on the growth of the promastigotes of Leishmania tropica minor, L. t. major, L. donovani and L. aethiopica.
By combining knowledge of polyamine biosynthesis and its inhibition by various analogues with that on the activity of synthetic anthraquinones, a series of six anthraquinone derivatives were synthesized. Their ability to inhibit the growth of leishmanial promastigotes in vitro was used as a preliminary screen to check their potential as new antileishmanial chemotherapeutics. They were tested against four strains, representing four different species; Leishmania tropica major, L. tropica minor, L. aethiopica and L. donovani, associated with four separate disease syndromes. All six derivatives exhibited a fair degree of antileishmanial activity, some being more effective than others. They all inactivated cultures at 100 micrograms/ml and some did so at 10 micrograms/ml and even 1 microgram/ml; but taking different lengths of time to achieve this. Antileishmanial activity associated with anthraquinone derivatives might provide a new approach to the chemotherapy of leishmaniasis.


Inhibition of Radiation and Temozolomide-Induced Invadopodia Activity in Glioma Cells Using FDA-Approved Drugs.
The most common primary central nervous system tumor in adults is the glioblastoma multiforme (GBM). The highly invasive nature of GBM cells is a significant factor resulting in the inevitable tumor recurrence and poor patient prognosis. Tumor cells utilize structures known as invadopodia to faciliate their invasive phenotype. In this study, utilizing an array of techniques, including gelatin matrix degradation assays, we show that GBM cell lines can form functional gelatin matrix degrading invadopodia and secrete matrix metalloproteinase 2 (MMP-2), a known invadopodia-associated matrix-degrading enzyme. Furthermore, these cellular activities were augmented in cells that survived radiotherapy and temozolomide treatment, indicating that surviving cells may possess a more invasive phenotype posttherapy. We performed a screen of FDA-approved agents not previously used for treating GBM patients with the aim of investigating their "anti-invadopodia" and cytotoxic effects in GBM cell lines and identified a number that reduced cell viability, as well as agents which also reduced invadopodia activity. Importantly, two of these, pacilitaxel and vinorelbine tartrate, reduced radiation/temozolomide-induced invadopodia activity. Our data demonstrate the value of testing previously approved drugs (repurposing) as potential adjuvant agents for the treatment of GBM patients to reduce invadopodia activity, inhibit GBM cell invasion, and potentially improve patient outcome.


Emergence of neural integration in the head-direction system by visual supervision.
Head-direction (HD) cells in subcortical areas of the mammalian brain are tuned to a particular head direction in space; a population of such neurons forms a neural compass that may be relevant for spatial navigation. The development of neural circuits constituting the head-direction system is poorly understood. Inspired by electrophysiological experiments about the role of recurrent synaptic connections, we investigate a learning rule that teaches neurons to amplify feed-forward inputs. We simulate random head movements of a rat, during which neurons receive both visual and vestibular (head-velocity) inputs. Remarkably, as recurrent connections learn to amplify exclusively the visual inputs, a neural network emerges that performs spatio-temporal integration. That is, during head movements in darkness, neurons resemble HD cells by maintaining a fixed tuning to head direction. The proposed learning rule exhibits similarities with known forms of anti-Hebbian synaptic plasticity. We conclude that selective amplification could serve as a general principle for the synaptic development of multimodal feedback circuits in the brain.


Somatosensory perception and cortical evoked potentials in established paraplegia.
In 66 patients who suffered severe spinal cord injury 7 months to 28 years previously, somatosensory cortical evoked potentials were recorded to electrical stimulation of the leg nerves and compared to clinical assessment of light touch, pain, position sense and two-point discrimination. The patients were separated into 4 categories according to the degree of disintegration of the somatosensory evoked potential waveform. A clear correlation was found between the impairment of somatosensory perception and the deterioration of the somatosensory evoked potential in each group. However, it was not possible to observe any direct correlation between the sensory score or impairment of a single modality and somatosensory evoked potential changes, or among the impairment of single modalities on a case by case basis. This study indicates that the somatosensory evoked potential can be used to provide electrophysiological information independent of the clinical examination on functions of the dorsal columns in the chronic stage of spinal cord injury.


NLRP3 is Required for Complement-Mediated Caspase-1 and IL-1beta Activation in ICH.
Complement-mediated inflammation plays a vital role in intracerebral hemorrhage (ICH), implicating pro-inflammatory factor interleukin-1beta (IL-1β) secretion. Brain samples and contralateral hemiencephalon were all collected and detected by Western blot. NLRP3 expression was located by dual immunofluorescence staining at 1, 3, and 5 days post-ICH. Brain water content was examined post-ICH. The neural deficit scores were evaluated by observers blindly. ILs were detected by ELISA. SiRNAs targeting NLRP3 (siNLRP3), siASC, and siControl were injected to inhibit NLRP3 function. To test the complement activation via Nod-like receptor (NLR) family pyrin domain-containing 3 (NLRP3), normal rabbit complement (NRC) was injected with lipopolysaccharide (LPS) to facilitate the complement function. As a result, complement 3a (C3a) and complement 5a (C5a) were upregulated during the ICH-induced neuroinflammation, and ablation of C3 attenuates ICH-induced IL-1β release. Though the LPS rescues the neuroinflammation in the ICH model, C3 deficiency attenuates the LPS-induced inflammatory effect. The NLRP3 inflammasome was activated after ICH and was located in the microglial cell of the mouse brain, which exhibits a time-dependent manner. However, the number of NLRP3/Iba-1 dual-labeled cells in the C3-/- group is less than that in the WT group in each time course, respectively. IL-1β and IL-18 released in perihematoma tissue, caspase-1-p20, brain water content, and behavioral outcomes were attenuated in the siNLRP3 and siASC groups than in the siControl and ICH groups. We also found that 5% of complement supplement enhances ICH-induced IL-1β release, while NLRP3 and ASC inhibition attenuates it. In conclusion, complement-induced ICH neuroinflammation depended on NLRP3 activation, which facilities LPS- and ICH-induced neuroinflammation, and NLRP3 is required for ICH-induced inflammation.


Ultrasound-Assisted Posteromedial Portal Placement of the Elbow Joint to Prevent Ulnar Nerve Injury.
Direct posterior and posterolateral portals are the standard portals used in posterior elbow arthroscopy. A posteromedial portal in the elbow is not recommended because of its proximity to the ulnar nerve. However, iatrogenic injuries to the ulnar nerve have been reported after elbow arthroscopy using the standard posterior portals, especially in posteromedial elbow joint pathologies. We present a surgical technique applicable to posteromedial elbow pathology by using ultrasound-assisted posteromedial portal placement of the elbow joint. Through this technique, the position of the ulnar nerve is identified prior to portal creation and the instruments are introduced from an ulnar to radial direction, thus avoiding ulnar nerve injury.


Gallic acid as a Sestrin (SESN2) activator and potential obesity therapeutic agent: A molecular docking study.
Sestrins (SESNs) are a family of evolutionarily conserved proteins among mammals. They have several body homeostatic functions such as antioxidant, metabolic, and anti-aging, and are required to regenerate hyperoxidized forms of peroxiredoxins and reactive oxygen species. Sestrin 2 has been studied as a therapeutic agent in obesity treatment. Gallic acid (GA) is a triphenolic compound with beneficial biological activities including anti-inflammatory, antidiabetic, antihypertensive, and antioxidant effects. Recent studies demonstrated the GA's ability to reduce body weight gain and improve glycemic parameters. In this sense, the present study aims to investigate the GA activating potential of Sestrin using the molecular docking method. The 3D structure of gallic acid was retrieved from the NCBI PubChem database and the chemical structure of the Sestrin2 protein from the RCSB Protein Data Bank (5DJ4). The docking calculus was performed via UCSF Chimera and AutoDock Vinaprograms. The results showed that amino acids Arg390, Glu451, Trp444, Thr386, Arg448, Thr374, Tyr375, Asn376, Thr377, Leu389, His454, Ser450, His86, and Val455 are very important for GA stabilization, resembling the interactions that permit Leucine to activate SESN2. In this context, the obesity therapeutic property of GA can be understood from a Sestrin activating process through amino acid metabolism.


Simultaneous traumatic bladder perforation and disruption of the prostatomembranous urethra.
The simultaneous occurrence of disruption of the prostatomembranous urethra and traumatic perforation of the bladder is seldom diagnosed before operation for the urethral injury. The presence of posterior disruption can make radiological diagnosis of the concomitant bladder perforation difficult. Lack of a palpable bladder a few hours after urethral injury should arouse suspicion of a combined injury. Careful bladder examination is indicated at the time of operation for all cases of posterior urethral injury to eliminate possible bladder perforations and the significant increase in morbidity and mortality associated with their presence.


Cathepsin B and L in nephron segments of rats with puromycin aminonucleoside nephrosis.
The intralysosomal proteinases, cathepsins B and L, were measured in microdissected segments of rat nephrons following a single injection of puromycin aminonucleoside (PAN). Z-Phenylalanyl-arginine-7-amido-4-methylcoumarin served as substrate. Enzyme activities, proteinuria, creatinine clearance and renal morphology were determined at specific time intervals following induction of PAN nephrosis. During the first three days following PAN injection, enzyme activities in S2 and S3 segments, protein excretion, creatinine clearance and appearance of the renal parenchyma resembled control animals. The enzyme activity in S1 segments was slightly decreased, but returned to control levels at day six after injection. Days four through eight post-PAN injection were characterized by a dramatic increase in protein excretion and an increase in cathepsin B and L activity in S2 and S3 segments of the proximal tubule. During days 9 through 15 enzyme activity decreased significantly in S2 segments despite continued proteinuria. Overt necrosis and cell injury were seen in the proximal tubule and probably account for the decrease in proteolytic activity. After day 15 following PAN injection, the level of proteinuria decreased, restoration of cathepsin activities occurred and a histopathologic picture of healing was present. The data suggest a positive relationship exists between stimulation of cathepsin B and L activity in S2 and S3 segments of the proximal tubule and increased protein filtration in PAN nephrosis. The increased enzyme activity reflects enhancement of the proteolytic capacity of the lysosomal system that is necessary for increased protein catabolism.


Advantage of magnetic resonance imaging in the diagnosis of cerebral infections.
18 patients with cerebral infections were investigated with a 1.5 Tesla-Magnetom. The results are compared to CT-findings obtained at the same time. In the majority of cases (n = 11) MR is superior to CT because it allows earlier detection of the disease, a more exact definition of the spread and a more detailed representation of complex inflammatory processes. MRI should rank first among all examination methods, especially in the determination of herpes simplex-encephalitis as it allows earlier detection and treatment of this disease.


Single Particle Dynamic Imaging and Fe3+ Sensing with Bright Carbon Dots Derived from Bovine Serum Albumin Proteins.
In this work, we demonstrated a convenient and green strategy for the synthesis of highly luminescent and water-soluble carbon dots (Cdots) by carbonizing carbon precursors, i.e., Bovine serum albumin (BSA) nanoparticles, in water solution. Without post surface modification, the as-synthesized Cdots exhibit fluorescence quantum yield (Q.Y.) as high as 34.8% and display superior colloidal stability not only in concentrated salt solutions (e.g. 2 M KCl) but also in a wide range of pH solutions. According to the FT-IR measurements, the Cdots contain many carboxyl groups, providing a versatile route for further chemical and biological functionalization. Through conjugation of Cdots with the transacting activator of transcription (TAT) peptide (a kind of cell penetration peptide (CPP)) derived from human immunodeficiency virus (HIV), it is possible to directly monitor the dynamic interactions of CPP with living cell membrane at single particle level. Furthermore, these Cdots also exhibit a dosage-dependent selectivity toward Fe(3+) among other metal ions, including K(+), Na(+), Mg(2+), Hg(2+), Co(2+), Cu(2+), Pb(2+) and Al(3+). We believed that the Cdots prepared by this strategy would display promising applications in various areas, including analytical chemistry, nanomedicine, biochemistry and so on.


Immune T cells can protect or induce fatal neurological disease in murine lymphocytic choriomeningitis.
Adoptively transferred immune spleen cells induce fatal neurological disease in cyclophosphamide-suppressed recipients injected intracerebrally (ic) with a large, but not small, dose of neurotropic lymphocytic choriomeningitis (LCM) virus. The elimination of virus from brain in the latter group, which survives without developing symptoms, depends upon the presence of Lyt 2+ lymphocytes. However removal of Lyt 2+ subset which is cytotoxic in vitro does not diminish the severity of the inflammatory process in vivo, though the onset of clinical disease is delayed in mice given Lyt 2-depleted populations and a larger ic dose of virus. The present findings are consistent with the idea that fatal LCM results from acute, synchronous damage to key functional cells in the central nervous system by virus-immune Lyt 2+, lymphocytes. Even so, if the number of virus-infected CNS cells is still relatively small at the time of T cell invasion, neurological symptoms are not recognized and the mice survive.


Determinants of nutritional status among children under age 5 in Ethiopia: further analysis of the 2016 Ethiopia demographic and health survey.
The aim of this study was to examine the determinants of nutritional status among children under age 5 (0-59 months) in Ethiopia. Child malnutrition is an underlying cause of almost half (45%) of child deaths, particularly in low socioeconomic communities of developing countries. In Ethiopia, the prevalence of stunting decreased from 47% in 2005 to 39% in 2016, but the prevalence of wasting changed little over the same time period (from 11 to 10%). Despite improvements in reducing the prevalence of malnutrition, the current rate of progress is not fast enough to reach the World Health Organization global target for reducing malnutrition 40% by 2025. This study used data from the 2016 Ethiopia Demographic and Heath Survey (EDHS). The analysis used stunting and wasting as dependent variables, while the independent variables were characteristics of children, mothers, and households. Logistic regression was used to analyze the determinants of nutritional status among children. Bivariate analysis was also used to analyze the association between the dependent and independent variables. Study results show that child's age, sex, and perceived birth weight, mother's educational status, body mass index (BMI), and maternal stature, region, wealth quintile, type of toilet facility, and type of cooking fuel had significant associations with stunting. Child's age, sex, and perceived birth weight, mother's BMI, and residence and region showed significant associations with wasting. The study found that child, maternal, and household characteristics were significantly associated with stunting and wasting among children under age 5. These findings imply that a multi-sectorial and multidimensional approach is important to address malnutrition in Ethiopia. The education sector should promote reduction of cultural and gender barriers that contribute to childhood malnutrition. The health sector should encourage positive behaviors toward childcare and infant feeding practices. More should be done to help households adopt improved types of toilet facilities and modern types of cooking fuels.


Observation of grain boundary plasmon and associated deconvolution techniques for low-loss electron energy-loss (EEL) spectra acquired from grain boundaries.
Spatially resolved valence electron energy-loss spectroscopy (VEELS) was used to acquire low-loss EEL spectra from Al grain boundaries (GBs) with different GB energies. The loss signal from the GB is highly delocalized and is mixed with the bulk loss, therefore requiring separation. Three different separation techniques, i.e., Fourier-log, Fourier-ratio deconvolution and direct subtraction, were employed to extract the GB response from the low-loss spectra and produced similar results. The GB response consists of a positive intensity peak from the excitation of GB plasmons (GBP) and a negative intensity begrenzungs (Bgs) peak from reduced scattering from bulk oscillations. Also, lower electron density at the GB reduces the inelastic scattering of the bulk plasmon. The intensity of GBP scattering and begrenzungs peak is found to increase toward the GBs, with maximum intensity when the electron probe is positioned on the GB, connecting the begrenzungs effect with the creation of a GBP.


Automatic patient table removal in CT images.
In many medical imaging applications, it is desirable and important to localize and remove the patient table from CT images. However, existing methods often require user interactions to define the table and sometimes make inaccurate assumptions about the table shape. Due to different patient table designs, shapes, and characteristics, these methods are not robust in identifying and removing the patient table. This paper proposes a new automatic approach which first identifies and locates the patient table in the sagittal planes and then removes it from the axial planes. The method has been tested successfully against different tables in different products from multiple vendors, showing it is both a versatile and robust technique for patient table removal.


Electron-beam CT: the effect of using a correction function on coronary artery calcium quantitation.
The purpose of the study was to determine if use of a correction function derived from a phantom with known calcium density reduces variation in coronary artery calcium scores measured with electron-beam computed tomography (CT) and to evaluate the influence of body girth, as measured by body mass index (BMI), on coronary artery calcium-score variability in a clinical screening cohort. Two hundred fifty consecutive patients underwent two electron-beam CT examinations with a standardized phantom. Region-of-interest (ROI) measurements of the phantom were correlated with the patient BMI. In a subset of 28 patients with low but positive coronary artery calcium scores, ROI values of the phantom were used as a correction for signal attenuation. Patient BMI was not significantly correlated to signal attenuation. Application of a correction function resulted in a small but insignificant decrease in interscan coronary artery calcium-score variation. The interscan coronary artery calcium score variation was 24.5% +/- 23.9; it decreased to 24.3% +/- 21.6 with use of the 75 mg/cm3 portion of the phantom and to 22.2% +/- 21.4 with use of the 150 mg/cm3 portion of the phantom. The use of a coronary artery calcium phantom does not reduce interscan variation sufficiently to warrant regular clinical usage. Interscan variation in the coronary artery calcium score is not significantly influenced by patient BMI.


The values of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in predicting 30 day mortality in patients with acute pulmonary embolism.
vAcute pulmonary embolism (PE) is a life threatening disease. The treatment options depend on the severity of the disease and the mortality varies widely depending on the severity of the condition. It is important to identify patients who are at high risk of mortality. The aim of the present study was to explore the prognostic alues of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) for 30-day mortality in patients with acute PE. The study included 321 patients admitted to our university hospital between January 2013 and May 2015 with the diagnosis of acute PE. Multivariable risk models were developed to assess the predictive values of the NLR and PLR for 30-day mortality. Discrimination was evaluated using receiver operating characteristic (ROC) curves. Two hundred forty-eight patients met our selection criteria. Twenty of them died within 30 days of hospital admission. NLR was found to be an independent predicator after other confounding factors were adjusted in the model. For 1 unit of increase of NLR, the risk of 30-day mortality rose about 13 % (OR = 1.13,95 % CI: 1.04-1.23). The area under ROC for NLR is 0.79 (95 %CI: 0.703-0.880). PLR was associated with 30-day mortality in univariate analysis but the predicative ability diminished with inclusion of other predicators in multivariable model. NLR is readily available predicator for short-term mortality. It could be a useful indicator for identifying high risk population and guiding clinical management of acute PE.


Interaction of the pioneer transcription factor GATA3 with nucleosomes.
During cellular reprogramming, the pioneer transcription factor GATA3 binds chromatin, and in a context-dependent manner directs local chromatin remodeling and enhancer formation. Here, we use high-resolution nucleosome mapping in human cells to explore the impact of the position of GATA motifs on the surface of nucleosomes on productive enhancer formation, finding productivity correlates with binding sites located near the nucleosomal dyad axis. Biochemical experiments with model nucleosomes demonstrate sufficiently stable transcription factor-nucleosome interaction to empower cryo-electron microscopy structure determination of the complex at 3.15 Å resolution. The GATA3 zinc fingers efficiently bind their target 5'-GAT-3' sequences in the nucleosome when they are located in solvent accessible, consecutive major grooves without significant changes in nucleosome structure. Analysis of genomic loci bound by GATA3 during reprogramming suggests a correlation of recognition motif sequence and spacing that may distinguish productivity of new enhancer formation.


Cervical dystonia: improved treatment response to botulinum toxin after referral to a tertiary centre and the use of polymyography.
Cervical dystonia is the most common form of (primary) dystonia. The first line of treatment for cervical dystonia is intramuscular injections with botulinum toxin. To optimise the response to botulinum toxin proper muscles selection is required. Pre-treatment polymyographic EMG in addition to clinical evaluation is hypothesised to be a good tool to improve muscle selection and treatment outcome. To determine the efficacy of botulinum toxin treatment after adjacent polymyographic EMG in cervical dystonia patients referred to our tertiary referral centre with an unsatisfactory response to botulinum toxin treatment elsewhere. We performed a retrospective analysis of 40 consecutive second opinion cervical dystonia patients. Standard polymyographic EMG was performed before treatment. We retrieved the Tsui scores and subjective evaluations from the first visit, after 12 weeks and after one year of treatment. In addition, we assessed the final outcome of treatment in our centre based on the records and asked the patients for their personal opinion about the effect of referral to our centre on their treatment response. After one year of treatment there was a significant improvement on both the Tsui scores (p < 0.01) and the subjective treatment evaluation (p < 0.001.) On their last visit 60% of the patients still continued treatment with a reasonable to good response. A substantial amount of CD patients with an unsatisfactory response to botulinum toxin improved after polymyography and subsequent treatment with botulinum toxin in a tertiary referral centre.


Treatment of keratoacanthoma with intralesional bleomycin.
Six patients with keratoacanthoma were successfully treated with intralesional injection of bleomycin. This new therapy produced a marked shortening of the clinical course without any complications.


Comprehensive Palliative Care Needs in Outpatients with Chronic Heart Failure: A Japanese Cross-Sectional Study.
The type and frequency of palliative care needs of chronic heart failure (CHF) patients have not been determined in Japan. The aim of this study was to comprehensively assess the prevalence and characteristics of palliative care needs of CHF outpatients. Patients were recruited for this cross-sectional study from June 1 to August 31, 2020, at the Kobe University Hospital. An Integrated Palliative care Outcome Scale (IPOS) and an original questionnaire developed by multidisciplinary experts were answered once by patients themselves or with the assistance of their family. A total of 101 patients (63 males and 38 females) were included. The most common distressing symptoms were dyspnea (29%; 95% confidence interval [CI] 21-39]), drowsiness (29%; 95% CI 21-39), poor mobility (25%; 95% CI 17-35), insomnia (25%; 95% CI 17-35), and anxiety (24%; 95% CI 17-35). Eighty percent (95% CI 70-87) of patients were willing to have an end-of-life (EOL) discussion. When we compared New York Heart Association class I/II with III/IV patients, the frequency of distressing symptoms was associated with the severity of the disease, but both groups exhibited a willingness for having an EOL discussion or knowing the future course of their diseases. Dyspnea, drowsiness, insomnia, and anxiety were frequent symptoms in CHF outpatients in Japan. Beyond distressing symptoms, most ambulatory heart failure patients have a need for EOL discussion, which was not associated with disease stage. Assessing comprehensive and multidimensional palliative care needs, including needs for EOL discussion, is advisable among outpatients with CHF.


Initiator-Activation Strategy-Enabled Organocatalyzed Reversible-Deactivation Radical Polymerization Driven by Light.
Organocatalyzed reversible-deactivation radical polymerizations (RDRPs) are attractive for many applications. Here, we developed photoredox-mediated RDRP by activating (hetero)aryl sulfonyl chloride (ArSO2 Cl) initiators with pyridines and designing a novel bis(phenothiazine)arene catalyst. The in situ formed sulfonyl pyridinium intermediates effectively promote controlled chain-growth from ArSO2 Cl, enabling access to various well-defined polymers with high initiation efficiencies and controlled dispersities under mild conditions. This versatile method allows "ON/OFF" temporal control, chain-extension, facile synthesis of different polymer brushes via organocatalyzed grafting reactions from linear chains. Time-resolved fluorescence decay studies and calculations support the reaction mechanism. This work provides a transition-metal-free RDRP to tailor polymers with readily available aromatic initiators, and will promote the design of polymerization leveraged from photoredox catalysis.


Double-blind, randomized, placebo-controlled 6-week study on the efficacy and safety of the tamoxifen adjunctive to lithium in acute bipolar mania.
Considerable amount of biochemical data supports the potential involvement of protein kinase C in the pathophysiology and treatment of bipolar disorder. The aim of this double-blind, placebo-controlled study was to investigate the efficacy and tolerability of tamoxifen as an adjunct to lithium for the treatment of acute mania in hospitalized bipolar patients. Eligible participants were 40 inpatients, between the ages of 19 and 49 years with current manic episode. Patients were randomly allocated to lithium (1-1.2 mEq/L) + tamoxifen 80 mg/day (group A) or lithium (1-1.2 mEq/L) + placebo (group B) for a 6-week, double-blind, placebo-controlled study. The principal measure of outcome was the Young Mania Rating Scale. The raters used standardized instructions for Young Mania Rating Scale. Young Mania Rating Scale scores improved with tamoxifen. The difference between the two protocols was significant as indicated by the effect of the group, the between-subjects factor (F=5.41, df=1, p=0.02). A significant difference was observed on the Positive and Negative Syndrome Scale total score at week 6 in the two groups. The difference between the two groups in the frequency of side effects was not significant except for fatigue that occurred more often in the tamoxifen group. Tamoxifen is an antagonist of estrogen receptor as well. The results demonstrate that the combination of tamoxifen with lithium was superior to lithium alone for the rapid reduction of manic symptoms. The combined use of tamoxifen with lithium was well tolerated in these acutely manic patients.


Black soldier fly (Hermetia illucens) larvae as potential feedstock for the biodiesel production: Recent advances and challenges.
Black soldier fly larvae (BSFL) Hermetia illucens is fastest growing and most promising insect species especially recommended to bring high-fat content as 5th generation bioenergy. The fat content can be fully optimized during the life-cycle of the BSFL through various organic dietary supplements and environmental conditions. Enriched fat can be obtained during the larval stages of the BSF. The presence of high saturated and unsaturated fatty acids in their body helps to produce 70 % of extractable oil which can be converted into biodiesel through transesterification. The first-generation biodiesel process mainly depends on catalytic transesterification, however, BSFL had 94 % of biodiesel production through non-catalytic transesterification. This increases the sustainability of producing biodiesel with less energy input in the process line. Other carbon emitting factors involved in the rearing of BSFL are less than the other biodiesel feedstocks including microalgae, cooking oil, and non-edible oil. Therefore, this review is focused on evaluating the optimum dietary source to produce fatty acid rich larvae and larval growth to accumulate C16-18 fatty acids in larger amounts from agro food waste. The process of optimization and biorefining of lipids using novel techniques have been discussed herein. The sustainability impact was evaluated from the cultivation to biodiesel conversion with greenhouse gas emissions scores in the entire life-cycle of process flow. The state-of-the-art in connecting circular bioeconomy loop in the search for bioenergy was meticulously covered.


Intravenous brexanolone for postpartum depression: what it is, how well does it work, and will it be used?
Postpartum depression is considered to be a subtype of major depressive disorder that occurs in approximately 10-20% of mothers worldwide. However, in actuality, these numbers are likely underreported due to minimization and the stigma of mental illness. Until recently, there were no approved medications for the treatment of postpartum depression. Allopregnanolone is a naturally occurring neuroactive steroid whose serum levels decline precipitously following childbirth. This hormonal fluctuation has been postulated as playing a role in the pathophysiology of postpartum depression. Brexanolone is the first medication approved by the US Food and Drug Administration for the treatment of postpartum depression. Brexanolone is an intravenous proprietary formulation of allopregnanolone that can be administered to produce stable serum levels comparable with third-trimester concentrations in postpartum mothers. It is hypothesized to modulate neuronal excitability by functioning as an allosteric modulator of γ-aminobutyric acid-A receptors and is administered under monitoring as a 60 h continuous infusion. In this review, we will highlight the results of the clinical trial program, including efficacy and tolerability data. Practical and logistical considerations of brexanolone will be reviewed, as will its potential place in therapy for the treatment of postpartum depression.


Comparison of Intra-articular Knee Injection of Corticosteroid between Hemodialysis and Non-hemodialysis Patients.
Hemodialysis patients have various complications, and orthopedic diseases include carpal tunnel syndrome, spinal canal stenosis, spondylosis destruction, fractures, and osteoarthritis. As a treatment for knee osteoarthritis, intra-articular injections of hyaluronic acid and steroids are performed. In general, steroid injections have a strong short-term anti-inflammatory effect, but there is a risk of complications, such as infection. In addition to aging, dialysis patients are prone to weakened immune systems and susceptibility to infection. Therefore, more attention should be paid to the treatment of osteoarthritis in dialysis patients. This study aimed to compare the effects of steroid and complication of infection of dialysis and non-dialysis patients who underwent intra-articular steroid injection. A total of 20 dialysis patients (23 knees) and 20 non-dialysis patients (24 knees) with knee osteoarthritis who underwent steroid injections were investigated. All patients underwent radiographic diagnosis and were evaluated for the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, visual analog scale (VAS), range of motion (ROM), and side effects before, and at 3, and 6 months after injection. The mean body mass index (BMI) was 21.3 (±standard deviation (SD) 2.8) and 24.9 (±SD 2.6) in dialysis and non-dialysis patients, respectively, showing a significant difference. Both dialysis and non-dialysis patients showed statistically significant improvement in VAS and WOMAC scores after steroid injection. There were no significant differences between dialysis and non-dialysis patients in the gender differences and mean age. There were no infection complications in both groups. This study revealed the analgesic effect of steroids on knee osteoarthritis in dialysis and non-dialysis patients. On the other hand, there were no infection complications in either patient. These findings suggest that intra-articular steroid injection is safe for dialysis patients.


Improvement of online monitoring of drinking water quality for the city of Prague and the surrounding areas.
In the article, a new method of continuous monitoring of the biological quality of raw and treated waters at the Želivka Water Treatment Plant is suggested and assessed. This water treatment plant is one of the largest water treatment plants in Europe and the largest water treatment plant in the Czech Republic with a maximum projected peak output of 7 m3.s-1 and current output of around 3 m3.s-1 of drinking water. It is the largest water treatment plant for Prague which is the capital city of the Czech Republic. Additionally, this water treatment plant also supplies drinking water to the Central Bohemia and Vysočina regions. The main intention of the research was to suggest a new system of monitoring, which can guarantee a more reliable continuous control of the safe drinking water supply for the city of Prague and the surrounding area. The suggested method represents a completely new approach to monitoring the biological quality of drinking water in the Czech Republic using the DaphTox apparatus, only two of which exist in the Czech Republic. The article describes the experience and knowledge gained during the operation of such a monitoring system, including a description of the necessary measures to ensure its proper operation with a focus on the pre-treatment of raw and chlorinated waters. Recommended simple pre-treatment methods secure optimal living conditions for monitoring organisms and have no impact on the original biological quality of monitored water which is a necessary condition for proper monitoring of biological quality.


Chikungunya fever in travelers returning to Europe from the Indian Ocean region, 2006.
Chikungunya fever has spread through several Indian Ocean islands and India, including popular travel destinations. To compare usefulness of diagnostic tests and to understand reasons for the magnitude and severity of an outbreak, we used 3 diagnostic methods to test 720 samples from 680 patients returning to Europe from the Indian Ocean region in 2006. Chikungunya infection was confirmed for 24.4% patients in the first half of the year and for 9.9% in the second half. Reverse transcription-PCR was positive for all samples taken up to day 4 after symptom onset. Immunofluorescence detected immunoglobulin (Ig) M on day 1 and IgG on day 2 for some patients, and in all patients from day 5 onward. Soon after onset of symptoms, patients had IgG and IgM and high viral loads (some >10(9) copies/mL plasma). These data will help healthcare providers select diagnostic tests for returning travelers.


Computational analysis of mixed cation mixed halide-based perovskite solar cell using SCAPS-1D software.
Standard MAPbI3 (MAPI) perovskite suffers from stability and toxicity problems. In this numerical simulation study using SCAPS-1D software, we propose a hybrid perovskite (MA1-x FA x Pb1-y Sr y I3) to reduce these effects; thus, the influence of the mixture of formamidinium (NH2CHNH 2 + (FA+)), strontium (Sr), methylammonium (CH3NH 2 + (MA+)) and lead (Pb) on the electrical parameters of a hybrid perovskite-based solar cell is studied. This simulation was performed through modeling the perovskite absorber band gap depending on x and y proportions. This mixture leads to increase the crystallinity or stability by decreasing MA+ proportion by FA+, while the toxicity is reduced by decreasing Pb2+ proportion by Sr2+. We show that the substitution of 90% MA and 15% Pb (MA0.1FA0.9Pb0.85Sr0.15I3) to the standard MAPI radically changes the electrical parameters of the material and the performance of the solar cell. A maximum efficiency of 29% ( J s c = 24.2 mA/cm2, V o c = 1.37 V, F F = 87.49 %) is obtained in this simulation of the hybrid perovskite-based solar cell. These results are obtained after optimizing the hybrid perovskite band gap (Eg = 1.60 eV), layer thicknesses (0.400 μm for hybrid perovskite, 0.250 μm for TiO2 ETL, and 0.150 μm for Cu2O HTL), absorber bulk defect density (1013 cm-3), and perovskite/TiO2 interface defects density (1012 cm-2). Our results show that the composition of MA, FA, Pb, and Sr in the MA1-x FA x Pb1-y SryI3 hybrid perovskite may be a way to obtain new perovskites with interesting physical properties for application in solar cells.


Predicting Drug Treatment Outcomes in Childrens with Tuberous Sclerosis Complex-Related Epilepsy: A Clinical Radiomics Study.
Highly predictive markers of drug treatment outcomes of tuberous sclerosis complex-related epilepsy are a key unmet clinical need. The objective of this study was to identify meaningful clinical and radiomic predictors of outcomes of epilepsy drug treatment in patients with tuberous sclerosis complex. A total of 105 children with tuberous sclerosis complex-related epilepsy were enrolled in this retrospective study. The pretreatment baseline predictors that were used to predict drug treatment outcomes included patient demographic and clinical information, gene data, electroencephalogram data, and radiomic features that were extracted from pretreatment MR imaging scans. The Spearman correlation coefficient and least absolute shrinkage and selection operator were calculated to select the most relevant features for the drug treatment outcome to build a comprehensive model with radiomic and clinical features for clinical application. Four MR imaging-based radiomic features and 5 key clinical features were selected to predict the drug treatment outcome. Good discriminative performances were achieved in testing cohorts (area under the curve = 0.85, accuracy = 80.0%, sensitivity = 0.75, and specificity = 0.83) for the epilepsy drug treatment outcome. The model of radiomic and clinical features resulted in favorable calibration curves in all cohorts. Our results suggested that the radiomic and clinical features model may predict the epilepsy drug treatment outcome. Age of onset, infantile spasms, antiseizure medication numbers, epileptiform discharge in left parieto-occipital area of electroencephalography, and gene mutation type are the key clinical factors to predict the epilepsy drug treatment outcome. The texture and first-order statistic features are the most valuable radiomic features for predicting drug treatment outcomes.


Serum Bioavailable, Rather Than Total, 25-hydroxyvitamin D Levels Are Associated With Hepatocellular Carcinoma Survival.
Free and bioavailable 25-hydroxyvitamin D (25OHD) are emerging measurements of vitamin D status. It remains unclear whether circulating free or bioavailable 25OHD are relevant to hepatocellular carcinoma (HCC) prognosis. Our aim was to test the hypothesis that bioavailable 25OHD may be a better serum biomarker of vitamin D status than total 25OHD on the association with HCC survival. We included 1,031 newly diagnosed, previously untreated patients with HCC from the Guangdong Liver Cancer Cohort enrolled between September 2013 and April 2017. Serum total 25OHD levels were measured using an electrochemiluminescence immunoassay. Serum-free 25OHD levels were measured using a two-step enzyme-linked immunosorbent assay. Bioavailable 25OHD levels were calculated from measured free 25OHD and albumin using a previously validated equation. Primary outcomes were liver cancer-specific (LCSS) and overall survival (OS). Cox proportional hazards models were performed to calculate the multivariable hazard ratios (HRs) and 95% confidence intervals (CIs). During a median follow-up of 726 days, 430 patients had deceased, including 393 deaths from HCC. In multivariable analyses, higher bioavailable 25OHD levels were significantly associated with better survival, independent of nonclinical and clinical prognostic factors including serum C-reactive protein, Barcelona Clinic Liver Cancer stage, and cancer treatment. The multivariable-adjusted HRs in the highest versus lowest quartile of bioavailable 25OHD levels were 0.69 (95% CI: 0.51, 0.93; P for trend = 0.014) for LCSS and 0.71 (95% CI: 0.53, 0.94; P for trend = 0.013) for OS. In contrast, neither total nor free 25OHD levels were associated with LCSS or OS. Higher bioavailable, rather than total, 25OHD levels were independently associated with improved survival in a population-based HCC cohort, suggesting a potential utility of bioavailable 25OHD in HCC prognosis.


A systematic review of the clinical relevance of repetitive transcranial magnetic stimulation.
Repetitive transcranial magnetic stimulation (rTMS) is an approved treatment for depression. The clinical relevance of its efficacy is unclear. The clinical relevance of findings in the rTMS literature was assessed by translating Hamilton Depression Rating Scale (HAMD) data into Clinical Global Impression-Improvement scale (CGI-I) scores. We performed electronic searches of MEDLINE, Embase, PsycINFO, PubMed and Cochrane Central Register of Controlled Trials for RCTs and non-RCT trials on rTMS using Hamilton Depression Rating Scale (HAMD). Articles were included if published in English before January 2014. We translated HAMD scores into nominal CGI-I scores for rTMS for depression and for treatment-resistant depression (TRD). About 960 abstracts were retrieved. Sixty-three studies were included, yielding 130 study arms. For depression, the mean percentage change in HAMD scores in all sham-controlled rTMS treatment arms was 35.63 (SD 16.35) and for sham-rTMS 23.33 (SD 16.51). For TRD, active rTMS in sham-controlled studies showed a mean HAMD percentage reduction of 45.21 (SD 10.94) versus 25.04 (SD 17.55) for sham-rTMS. When aggregated scores were translated into notional CGI-I scores, for the treatment of depression, the notional CGI-I score difference between rTMS and sham-rTMS was 0.5 in favour of rTMS; for TRD, it was 0.75 in favour of rTMS. Differences between rTMS and sham-rTMS were bigger when all study arms were combined. Whilst rTMS appears to be efficacious for both non-refractory and treatment-resistant depression, the clinical relevance of its efficacy is doubtful.


Comparative neurotoxicity of dietary methylmercury and waterborne inorganic mercury in fish: Evidence of optic tectum vulnerability through morphometric and histopathological assessments.
This work investigated the effects of inorganic mercury (iHg) and methylmercury (MeHg) on the fish optic tectum morphology, viz. in relation to: (i) vulnerability of specific optic tectum layers; (ii) preferential targeting of Hg forms to neurons or glial cells; (iii) comparative toxicity of iHg and MeHg in this brain area that is in the maintenance of several fish behaviors. Two experiments exposing juvenile white seabream (Diplodus sargus) to waterborne iHg [HgCl2 (2 μg L-1)] and dietary MeHg (8.7 μg g-1) were performed, comprising both exposure (7 and 14 days; E7 and E14, respectively) and post-exposure (28 days; PE28) periods. Morphometric assessments were performed using stereological methods where the layers of the optic tectum were outlined, while its area and the number of neurons and glial cells were estimated. A histopathological assessment was also performed per section and per layer of optic tectum. iHg exposure did not trigger the loss of neurons during the exposure periods, while a decrease of glial cells was detected in a single layer of the optic tectum at E14. Differently, upon MeHg exposure, a decrease on the number of neurons and glial cells was found in several layers of optic tectum. In the post-exposure, both Hg forms triggered the loss of neurons, while only MeHg exposure led to a decrease on the number of glia cells. The histopathological assessment pointed out a higher toxicity of MeHg in the optic tectum layers, particularly in the post-exposure period, while no significant alterations were found in fish exposed to iHg. Hg forms targeted preferentially neurons. iHg and MeHg are relevant neurotoxicants to fish, with MeHg exposure leading to a higher toxicity than iHg in the optic tectum. After 28 days of post-exposure, iHg and MeHg neurotoxicity remained prominent, suggesting long-term effects of these toxicants.


Neuromuscular disorders and 2010: recent advances.
This short review summarises the research articles related to neuromuscular disorders published in the Journal of Neurology over the last year from May 2009 to July 2010.


The effects of elevated CO2, elevated O3, elevated temperature, and drought on plant leaf gas exchanges: a global meta-analysis of experimental studies.
Global change significantly influences plant leaf gas exchange, which affects the carbon-water cycle of terrestrial ecosystems. However, the magnitudes of the effects of multiple global change factors on leaf gas exchanges are currently lacking. Therefore, a global meta-analysis of 337 published articles was conducted to determine the effects of elevated CO2 (eCO2), elevated O3 (eO3), elevated temperature (eT), and drought on plant leaf gas exchanges. The results indicated that (1) the overall responses of photosynthesis rate (Pn) and instantaneous water use efficiency (WUEi) to eCO2 increased by 28.6% and 58.6%. But transpiration rate (Tr) and stomatal conductance (gs) responded negatively to eCO2 (- 17.5% and - 17.2%, respectively). Furthermore, all Pn, gs, and WUEi responded negatively to eO3 (- 32.7%, - 24.6%, and - 27.1%), eT (- 23.2%, - 10.8%, and - 28.9%), and drought (- 53.6%, - 59.3%, and - 4.6%, respectively), regardless of functional groups and various complex experimental conditions. (2) Elevated CO2 increased WUEi combined with eO3, eT, and drought (26.6%, 36.0%, and 58.6%, respectively, for eCO2 + eO3, eCO2 + eT, and eCO2 + drought) and mitigated their negative impacts on Pn to some extent. (3) Plant form and foliage type play an important role in the responses of leaf gas exchanges. Trees responded mostly to eCO2, but responded least to eT in Pn, Tr, gs, and WUEi compared with shrubs and herbs. Evergreen broad-leaved species were more responsive to eCO2 and drought. (4) The stress level of each factor can also significantly influence the responses of leaf gas exchanges to environment change. Hopefully, the quantitative results are helpful for the further assessments of the terrestrial carbon-water cycle.


Pharmacokinetic study of rifampicin in biliary surgery.
Following the oral administration of 600 mg rifampicin, the concentration of antibiotic in serum, bile of the gallbladder and choledochus, cholecystic wall, and hepatic tissue was determined with the agar diffusion method in 23 patients undergoing surgery for cholelithiasis. After 80-340 minutes the average rifampicin concentration was 6.4 microgram/ml in serum, 78.4 microgram/ml in the bile of the gallbladder, 91.6 microgram/ml in the bile of the choledochus, 4.0 microgram/g in the cholecystic wall, and 23.3 microgram/g in the hepatic tissue. After 24 hours the level was significantly reduced in the serum and hepatic tissue. The rifampicin level in the bile of the gallbladder was twelvefold, in the bile of the choledochus fourteenfold, in the cholecystic wall 61.1% and in the hepatic tissue 364% of the serum level. In general, the rifampicin concentration obtainable in the bile and hepatic tissue is sufficient against bacterial strains causing infections of the biliary duct, and for this reason rifampicin will play in the future an important role in the treatment of infections of the biliary duct.


Familial transmission of seasonal changes in sleep and eating function in the general population.
Both genetic and environmental factors may be involved in the development of the increased sleep and appetite/body weight during winter, which are observed in seasonal affective disorder (SAD) as well as in normal variants of behavior in the general population. Decreases of these psychosomatic functions are also observed during summer, although the change may be less apparent than the winter changes. We studied familial correlation of these seasonal changes in 129 small Japanese families of the general population, using the Seasonality Pattern Assessment Questionnaire (SPAQ). No association was observed between the child and biological parents in the changes of sleep length or appetite/body weight during winter or summer. In contrast, significant spouse correlations were found in the changes of sleep and eating function during winter as well as during summer. This may indicate a role of shared environmental factors in the development of the seasonal patterns. The present results are preliminary and further studies are recommended.


Evolution of clinical, histological and serological features in a Primary Sjὄgren´s Syndrome cohort and the limitations of the current classification criteria.
The classification and/or diagnosis of Primary Sjögren's Syndrome (PSS) requires a multidimensional approach. Although age and the duration of sicca symptoms can affect the clinical, serological and histological features found at initial evaluation, these are not considered when using classification criteria as a guide for PSS diagnosis. Our study aimed to explore if there is any relationship between the duration of symptoms and clinical, histopathological and serological findings. An observational, retrospective study was performed. All the evaluated subjects were part of the "sicca cohort". Patients' clinical, serological and histological characteristics were assessed according to the duration of symptoms. A Receiving Operator Characteristic (ROC) curve was performed to establish the duration of symptoms (months) that predicted a PSS diagnosis. Binary regression models and odds ratios were used to evaluate the association between the duration of symptoms and the clinical, serological, and histopathological profiles. One hundred and sixteen patients were included; 97(83.62%) fulfilled PSS criteria. Of the 116 patients, thirty-six (31.03%) had < 15 months presenting with sicca symptoms when receiving a diagnostic approach. A duration of symptoms >15 months was associated with an altered Schirmer test (OR 2.76; 95% CI 1.15-6.61, P=0.02), low salivary flow rate (OR 3.5; 95% CI 1.34-9.13, P=0.01), ≥1 foci score (OR 1.21; 95% CI 1-1.45, P=0.04), ocular (OR 7.8; 95% CI 1.49-40.81, P=0.02) and severe oral symptoms (OR 2.61; 95% CI 1.16-5.87, P=0.02). The time of evolution of symptoms plays a fundamental role in the clinical, histological and serological profiles in PSS.


Ionic liquid recovery and recycling via electrodialysis in biomass processing: An economical assessment.
Extravagant price and lack of high-efficiency recovery technology limited scale-up utilization of ionic liquids. Ionic liquids recovery with electrodialysis-based techniques has caught wide concern due to membrane-based characteristic. Economical assessment for electrodialysis-based ionic liquid recovery and recycling in biomass processing was performed by determining influence of equipment-related and financial-related factors with sensitivity analysis for each factor. Overall recovery cost of 1-ethyl-3-methylimidazolium acetate, choline acetate, 1-butyl-3-methylimidazolium hydrogen sulphate and 1-ethyl-3-methylimidazolium hydrogen sulfate varied within 0.75-1.96 $/Kg, 0.99-3.00 $/Kg, 1.37-2.74 $/Kg and 1.15-2.89 $/Kg when factors changed within investigated range. Fold of membrane cost, factor of membrane stack cost, factor of auxiliary equipment cost, factor of annual maintenance cost and annual interest rate of loan were positively related with recovery cost. While percentage of annual elapsed time and loan period were negatively correlated with recovery cost. Economical assessment confirmed economic efficiency of electrodialysis for ionic liquids recovery and recycling in biomass processing.


Differences in preservation of canine chilled semen using different transport containers.
In the present study, the effect of three different containers in the preservation of dog chilled semen, during 24, 48 and 72h was evaluated. Weekly sperm pools of different dogs were obtained, during 10 consecutive weeks. Semen samples were diluted in egg-yolk-Tris-fructose extender and stored in a Styrofoam box, a common Thermos flask and an Equitainer. Progressive motility, morphology and sperm membrane integrity were examined in semen aliquots taken daily from each container during the 3 days of storage. Additionally, integrity of the acrosome and sperm plasma membranes, determined by PI/Fitc-PSA staining was assessed at 48 and 72h of storage. At 24h no differences were observed between the three containers for the evaluated parameters. At 48h samples kept in the Equitainer presented a higher progressive motility than samples kept in the Thermos. At 72h, progressive motility was higher in the Equitainer than in the other two containers. Only samples kept in the Equitainer maintained similar levels of progressive motility between 24 and 72h. Membrane integrity assessed by eosin-nigrosin deteriorated over the 72h period, whereas functional membrane integrity determined by the hypoosmotic swelling test was independently affected by type of container (the Equitainer) kept a higher percentage of sperm cells with intact membrane) and time of storage (a decrease of membrane integrity between 24 to 72h). Staining with PI-Fitc-PSA allowed the detection of differences between containers but not between the two studied storage periods (48 and 72h). The results indicated that the use of the Equitainer is preferable when transporting chilled dog semen for more than 48h.


Noradrenergic Signaling and Neuroinflammation Crosstalk Regulate Toxoplasma gondii-Induced Behavioral Changes.
Infections of the nervous system elicit neuroimmune responses and alter neurotransmission, affecting host neurological functions. Chronic infection with the apicomplexan parasite Toxoplasma correlates with certain neurological disorders in humans and alters behavior in rodents. Here, we propose that the crosstalk between neurotransmission and neuroinflammation may underlie some of these cognitive changes. We discuss how T. gondii infection suppresses noradrenergic signaling and how the restoration of this pathway improves behavioral aberrations, suggesting that altered neurotransmission and neuroimmune responses may act in concert to perturb behavior. This interaction might apply to other infectious agents, such as viruses, that elicit cognitive changes. We hypothesize that neurotransmitter signaling in immune cells can contribute to behavioral changes associated with brain infection, offering opportunities for potential therapeutic targeting.


Rab27b promotes endometriosis by enhancing invasiveness of ESCs and promoting angiogenesis.
Endometriosis (EMS) is an estrogen-dependent disease which is characterized with estrogen-dependent growth of ectopic endometrium and increased local estrogen production. EMS performs tumor-like biological functions such as invasiveness and angiogenesis. Rab27b is a member of the Rab family of GTPases, which is strongly associated with the growth, invasion and metastasis of a variety of tumors. However, little is known about the function of Rab27b in EMS. In this study, we intended to investigate the impact of Rab27b and its downstream molecule in the development of EMS. Normal endometrium and endometriotic lesions were collected to investigate the expression levels of Rab27b. Then, ESCs were transfected with Rab27b siRNA. We analyzed the influence of Rab27b on the proliferation and invasive activity of ESCs. Conditioned media harvested from Rab27b siRNA-treated ESCs were used to treat HUVECs. HUVEC Tube formation and ELISA were performed to explored the interactions between ESCs and HUVEC. In addition, ESCs were treated with different concentrations of estrogen. Based on biological database predictions, we explored possible mechanisms through which estrogen regulates the expression of Rab27b. The expressions of Rab27b were significantly higher in endometriotic lesions than that in normal endometrium. Rab27b can promote the cell proliferation, migration and invasion of ESCs. The elevated expression of Rab27b, on the one hand, promotes the secretion of MMP9 and increases the invasiveness of ESCs. On the other hand, Rab27b may play a key role in the communication between ESC and endothelial cells, by simulating VEGF secretion and neovascularization. Besides, estrogen upregulated phosphorylated FOXO1 levels in ectopic ESCs, resulting in the promotion of Rab27b expression levels. Rab27b plays a key role in the development of EMS, which may provide new insights into the pathogenesis of EMS. Our findings may also contribute to the development of therapeutic interventions for EMS.


Dorsal striatal dopamine induces fronto-cortical hypoactivity and attenuates anxiety and compulsive behaviors in rats.
Dorsal striatal dopamine transmission engages the cortico-striato-thalamo-cortical (CSTC) circuit, which is implicated in many neuropsychiatric diseases, including obsessive-compulsive disorder (OCD). Yet it is unknown if dorsal striatal dopamine hyperactivity is the cause or consequence of changes elsewhere in the CSTC circuit. Classical pharmacological and neurotoxic manipulations of the CSTC and other brain circuits suffer from various drawbacks related to off-target effects and adaptive changes. Chemogenetics, on the other hand, enables a highly selective targeting of specific neuronal populations within a given circuit. In this study, we developed a chemogenetic method for selective activation of dopamine neurons in the substantia nigra, which innervates the dorsal striatum in the rat. We used this model to investigate effects of targeted dopamine activation on CSTC circuit function, especially in fronto-cortical regions. We found that chemogenetic activation of these neurons increased movement (as expected with increased dopamine release), rearings and time spent in center, while also lower self-grooming. Furthermore, this activation increased prepulse inhibition of the startle response in females. Remarkably, we observed reduced [18F]FDG metabolism in the frontal cortex, following dopamine activation in the dorsal striatum, while total glutamate levels- in this region were increased. This result is in accord with clinical studies of increased [18F]FDG metabolism and lower glutamate levels in similar regions of the brain of people with OCD. Taken together, the present chemogenetic model adds a mechanistic basis with behavioral and translational relevance to prior clinical neuroimaging studies showing deficits in fronto-cortical glucose metabolism across a variety of clinical populations (e.g. addiction, risky decision-making, compulsivity or obesity).


Molecular characterization of carbapenem-resistant Klebsiella pneumoniae in a tertiary university hospital in Turkey.
The aim of this study was to identify the resistance genes and genetic relationship of carbapenemase-resistant Klebsiella pneumoniae (CRKP) identified in a tertiary university hospital in Turkey. During the study, CRKP was isolated from 137 patients. Resistance genes were studied in 94 isolates. Among these isolates, most of the CRKP produced only oxacillinase (OXA)-48 (91.5%); however, 4.3% of the isolates produced only New Delhi metallo-beta-lactamase 1 (NDM-1), 1% produced both OXA-48 and NDM-1, and 3.2% produced imipenem. This study adds Turkey to the growing list of countries with NDM-1-producing bacteria and shows that NDM-1 may easily spread worldwide.


Disruption of gene expression and induction of apoptosis in prostate cancer cells by a DNA-damaging agent tethered to an androgen receptor ligand.
The goal of our work was the design of DNA-damaging agents that disrupt both DNA repair and signaling pathways in prostate tumor cells. A DNA alkylator (N,N-bis-2-chloroethyl aniline) was linked to a steroid ligand (17beta-hyroxy-estra-Delta(4(5),9(10))-3-one) to produce a complex molecule (11beta-dichloro) that forms DNA adducts that bind the androgen receptor (AR). We speculated that DNA adducts in an AR-DNA adduct complex would be camouflaged from DNA repair proteins that would otherwise remove the adducts in prostate cancer cells. Furthermore, transcription dependent on the AR would be antagonized by AR redistribution to sites distant from AR-driven promoters. The anticancer potential of 11beta-dichloro was demonstrated against prostate cancer cells in vitro and in vivo. 11beta-dichloro induces a unique pattern of gene disruption, induces apoptosis in apoptosis-resistant cells, and shows promising anticancer activity in animals.


[Management of acquired urethral stricture: our experience in the Division of General Surgery in Sikasso].
Urethral stricture is a disease whose cause and management vary according to the context. This study aims to analyze the epidemiological etiological and therapeutic features of urethral stricture in our department. We conducted a longitudinal cross-sectional study of patients with acquired urethral stricture admitted to our department between March 2014 and February 2016. The average age of our patients was 24.5 years (10 and 81years). The diagnosis was confirmed by retrograde and voiding Urethro-Cystography (UCG). The average stricture length was 2.28cm (0.5-5cm). The therapeutic approaches included: resection with termino-terminal anastomosis; retrograde dilatation etc. Outcome assessment performed 6-15 months after surgery was satisfactory with absence of recidivism, PMR ≤30cc and strong urine flow and weak in the case of recurrence of dysuria or PMR ≥100cc. Urethral stricture accounted for 7.14% of our urologic treatments. Most of our patients were farmers from the rural area. A history of recurrent urethritis was most often reported by our patients and 78,57% of them were married men, among whom 91% were polygamous). The main reason for consultation was dysuria (50% of the study population) and 50.01% of our patients had secondary urinary tract infection, most commonly caused by Escherichia coli. The main cause of urethral stricture was an infection (56.52%). The most affected area was the bulbar urethra (45.60% of cases). UCG was the most used technique (39.13%). Overall outcomes were good (85,65%) and failure rate reached 13.04%; the highest success rate was achieved with resection with anastomosis (94.44% respectively). Urethral stricture is common among young people. Infection is the main cause in our department. Prevention is essential as well as an efficient and effective management of sexually transmitted infections.


Mechanism of inhibition of renin release by clonidine in rats.
In anaesthetized rats, the intracisternal injection of clonidine (1 microgram/kg) reduced mean arterial pressure (MAP), increased plasma renin concentration (PRC) while naphazoline (5 microgram/kg) was ineffective. The i.v. administration of clonidine (30 microgram/kg) still lowered MAP, but in this case, the drug decrease PRC, naphazoline (45 microgram/kg, i.v.) also reduced PRC. It is suggested that i.v. clonidine and naphazoline reduce renin release through activation of alpha-adrenoceptors within the kidney.


Development of SYN-004, an oral beta-lactamase treatment to protect the gut microbiome from antibiotic-mediated damage and prevent Clostridium difficile infection.
The gut microbiome, composed of the microflora that inhabit the gastrointestinal tract and their genomes, make up a complex ecosystem that can be disrupted by antibiotic use. The ensuing dysbiosis is conducive to the emergence of opportunistic pathogens such as Clostridium difficile. A novel approach to protect the microbiome from antibiotic-mediated dysbiosis is the use of beta-lactamase enzymes to degrade residual antibiotics in the gastrointestinal tract before the microflora are harmed. Here we present the preclinical development and early clinical studies of the beta-lactamase enzymes, P3A, currently referred to as SYN-004, and its precursor, P1A. Both P1A and SYN-004 were designed as orally-delivered, non-systemically available therapeutics for use with intravenous beta-lactam antibiotics. SYN-004 was engineered from P1A, a beta-lactamase isolated from Bacillus licheniformis, to broaden its antibiotic degradation profile. SYN-004 efficiently hydrolyses penicillins and cephalosporins, the most widely used IV beta-lactam antibiotics. In animal studies, SYN-004 degraded ceftriaxone in the GI tract of dogs and protected the microbiome of pigs from ceftriaxone-induced changes. Phase I clinical studies demonstrated SYN-004 safety and tolerability. Phase 2 studies are in progress to assess the utility of SYN-004 for the prevention of antibiotic-associated diarrhea and Clostridium difficile disease.


Effects of supramaximal exercise on the electromyographic signal.
To determine the neuromuscular recruitment characteristics during supramaximal exercise. Ten healthy subjects completed the Wingate anaerobic test (WAT) cycling protocol. Electromyographic (EMG) data and rate of fatigue were recorded throughout the cycling. The mean (SD) rate of fatigue (decrease in power output) was 44.5 (8.6)%. No significant change was found in EMG amplitude. A significant decrease (p<0.01) in mean power frequency spectrum was found over the 30 second period. During WAT, mean power frequency spectrum was attenuated with no decline in EMG amplitude, which may be caused by an accumulation of metabolites in the periphery. However, it is also possible that the feedback loop from intramuscular metabolism to the central nervous system is unable, within the 30 second period of the WAT, to affect neural recruitment strategy.


Chondrocyte-derived Exosomal miR-195 Inhibits Osteosarcoma Cell Proliferation and Anti-Apoptotic by Targeting KIF4A in vitro and in vivo.
Osteosarcoma (OS) is a primary malignant tumor of the bone that occurs in adolescents and is characterized by a young age at onset, high malignancy, high rate of metastasis, and poor prognosis. However, the factors influencing disease progression and prognosis remain unclear. In this study, we aimed to investigate the role of chondrocyte-derived exosomal miR-195 in OS. We used normal human chondrocytes to form miR-195-carrying exosomes to deliver miR-195 into OS cells. Xenograft tumor experiments were performed in mice intratumorally injected with exosomal miR-195. We found that kinesin superfamily protein 4A (KIF4A) promoted OS tumor progression and anti-apoptotic. We demonstrated that miR-195 inhibited the expression of KIF4A by directly targeting its 3'-untranslated region. Moreover, we observed that exosomal miR-195 successfully inhibited OS cell tumor growth and antiapoptotic in vitro and suppressed tumor growth in vivo. Collectively, these results demonstrate that normal human chondrocyte-derived exosomal miR-195 can be internalized by OS cells and inhibit tumor growth and antiapoptotic by targeting KIF4A, providing a new direction for clarifying the molecular mechanism underlying OS development.


Layered by layered construction of three novel ZnCo-LDHs/g-C3N4 for the removal of sunset yellow by adsorption-photocatalytic process.
The removal of organic dyes has attracted attention by adsorption-photocatalytic synergetic process in water treatment technology. Three novel ZnCo-LDHs/g-C3N4 were successfully prepared for the first time by layered construction technique through the hydrolysis of triethanolamine in this paper. They exhibited high specific surface area which facilitates the adsorption of sunset yellow (SY) from solution to catalyst surface. All the target pollutant dyes are very effectively removed by the three ZnCo-LDHs/g-C3N4 composites through synergetic effect of adsorption and photocatalysis process under UV irradiation (λ = 365 nm). The order of synergistic degradation effect for SY is as follows: ZnCo-LDHs/g-C3N4-3 (99.6%) > ZnCo-LDHs/g-C3N4-2 (99.5%) > ZnCo-LDHs/g-C3N4-1 (99.3%) > pure g-C3N4 (77.4%) > pure ZnCo-LDHs (44.2.6%) at the initial concentration of 75 mg L-1. ZnCo-LDHs/g-C3N4-3 has the largest k value (0.0284 min-1) in SY degradation, which is 2.8 times that of g-C3N4. ZnCo-LDHs/g-C3N4-3 is a very promising adsorption-photocatalyst for the removal of SY from wastewater. The electron spin resonance experiments demonstrate that OH·, 1O2, and O2- are the dominant active species and oxides SY together. This result demonstrates that the three ZnCo-LDHs/g-C3N4 have practical applications as efficient adsorption-photocatalytic materials and also provides a synergetic strategy for the removal of SY wastewater.


Specificity of lipoprotein lipase binding to endothelial cells.
Lipoprotein lipase (LPL) hydrolyzes circulating lipoprotein triglyceride molecules while it is associated with the luminal surface of capillary endothelial cells. The precise molecular mechanism by which LPL attaches to these cells is unknown. LPL and a number of other molecules, including growth factors and clotting factors, bind to heparin-affinity gels and are eluted using high concentrations of salt. Of these molecules, antithrombin III and basic fibroblast growth factor have been shown to bind to specific cell surface heparan sulfate proteoglycans. Recent data from our laboratory (Sivaram et al. 1992. J. Biol. Chem. 267: 16517-16522) have shown that a heparin-sensitive, non-proteoglycan 116-kDa LPL-binding protein is present on cultured bovine aortic endothelial cells (BAEC). A series of experiments was performed to study the specificity of LPL binding to BAEC and to this 116-kDa protein. At low amounts of LPL (1 microgram) 125I-labeled LPL binding to the cells was inhibited up to 82% by the addition of a 20-fold excess of unlabeled LPL. LPL binding to the BAEC was not decreased by the addition of similar amounts of either antithrombin or thrombin. Specific LPL binding was eliminated by incubating the BAEC at 4 degrees C with heparin containing buffer prior to the addition of LPL. Although cellular internalization of 125I-labeled LPL at 37 degrees C was decreased when an excess of each of the three proteins was added to the culture medium, LPL was most effective. Furthermore, when LPL interaction with the 116-kDa binding protein was studied using ligand blots, 125I-labeled LPL binding was blocked only by unlabeled LPL.(ABSTRACT TRUNCATED AT 250 WORDS)


Prevention of spinal epidural fibrosis by recombinant tissue plasminogen activator in rats.
A randomized-controlled experimental study was conducted to investigate the effectiveness of recombinant tissue plasminogen activator (rt-PA) on postlaminectomy epidural fibrosis in rats. Diyarbakir, Turkey. In a rat model, allowing objective histopathological quantification, the postoperative epidural scar formation was investigated and the potential of local rt-PA in preventing the production of epidural fibrosis was assessed. Rats were randomly allocated to local rt-PA (12 rats) or control (12 rats). Findings suggest a beneficial effect of rt-PA in decreasing the epidural fibrosis following laminectomy when compared with control groups for all investigated parameters such as intermuscular scar (P=0.04), middle scar (P=0.001), deep scar (P=0.001) and dural adhesion (P=0.01) except new bone formation. The presence of arachnoiditis was less in treatment group (P=0.01). In rats, the topical thrombolysis with rt-PA is safe and efficacious in preventing postlaminectomy epidural fibrosis. This Thrombolytic therapy with rt-PA after spine surgery may come to play an important role in the prevention of epidural fibrosis and arachnoiditis.


Injury as disease.
Consideration of injury as disease is an arbitrary distinction that nonetheless may have some utility. The disease concept includes the understanding that the agents and mechanisms of human/environmental interaction for injury causation are similar to those for many of the chronic diseases, with differences in the timing rather than the agent or mechanism of the transmission. As with other aspects of medical practice, injury control requires careful and knowledgeable epidemiologic, technological, psychological and social planning, and equally careful and knowledgeable attention to proper evaluation of intervention programs. Such evaluation has rarely been attempted with behavioral interventions but has been carried out somewhat more often with environmental countermeasures. Evaluation of both costs and benefits must include attention to factors that often cannot be measured in economic terms and that may differ not only in degree but in kind. Therefore, no methods for comparability may exist at this time for some of these costs and effects.


Task by stimulus interactions in brain responses during Chinese character processing.
In the visual word recognition literature, it is well understood that various stimulus effects interact with behavioral task. For example, effects of word frequency are exaggerated and effects of spelling-to-sound regularity are reduced in the lexical decision task, relative to reading aloud. Neuroimaging studies of reading often examine effects of task and stimulus properties on brain activity independently, but potential interactions between task demands and stimulus effects have not been extensively explored. To address this issue, we conducted lexical decision and symbol detection tasks using stimuli that varied parametrically in their word-likeness, and tested for task by stimulus class interactions. Interactions were found throughout the reading system, such that stimulus selectivity was observed during the lexical decision task, but not during the symbol detection task. Further, the pattern of stimulus selectivity was directly related to task difficulty, so that the strongest brain activity was observed to the most word-like stimuli that required "no" responses, whereas brain activity to words, which elicit rapid and accurate "yes" responses were relatively weak. This is in line with models that argue for task-dependent specialization of brain regions, and contrasts with the notion of task-independent stimulus selectivity in the reading system.


Quantification of Malalignment and Corrective Osteotomies in Patients With Malunion After Elastic Stable Intramedullary Nailing of Pediatric Forearm Fractures.
This study looked at postoperative malunion with restricted function after elastic stable intramedullary nailing (ESIN) in pediatric patients in their childhood or adolescence. The primary objective was to compare the magnitude of the osseous malposition to the healthy opposite side. Second, these individuals were treated with patient-specific surgical instrumentation, and functional outcomes were documented. Patients under the age of 18 at the time of a corrective osteotomy due to a forearm malunion after initial ESIN treatment were included in this study. The healthy contralateral side was used as a reference for preoperative analysis and planning of the osteotomy. Osteotomies were performed using patient-specific guides and the direction and extent of the malunion were compared to the change in range of motion (ROM) after the operation. Fifteen patients met the inclusion criteria at three years after initial ESIN placement, with the most pronounced malposition in the rotational axis. The postoperative function significantly improved by 12° (pre-op: 60° ± 17; post-op: 72° ± 10) of pronation and 33° (pre-op: 43° ± 26; post-op: 76° ± 13) of supination. There was no correlation between the amount and direction of malformation and the change in ROM. The most noticeable malunion after forearm fractures treated with the ESIN technique is in the rotational direction. Patient-specific corrective osteotomy of pediatric forearm malunion following forearm fracture fixation with ESIN achieves significant improvement in forearm range of motion. The findings are clinically relevant since forearm fractures are the most common pediatric fracture, affecting a large number of patients who can benefit from the findings of this study. It has the potential to raise awareness of the significance of the accurate rotational component of intraoperative bone alignment in the ESIN procedure.


[The predictive value of urinalysis in the New Dutch Kidney Test].
A urine test is described, by which a reliable indication of the time of slaughter is obtained in normal as well as in diseased animals, in which the New Netherlands Kidney Test (NNKT) will be negative. The test plate and testing procedure of the NNKT are used in this urine test.


The effects of the three-dimensional active trunk training exercise on trunk control ability, trunk muscle strength, and balance ability in sub-acute stroke patients: A randomized controlled pilot study.
Trunk control ability has been identified as an important early predictor of functional recovery after stroke. Our study aimed to investigate the effects of three-dimensional active trunk training exercise on trunk control ability, trunk muscle strength, and balance ability in sub-acute stroke patients. Twenty-four sub-acute stroke patients were randomly assigned to an experimental (n= 12) or control (n= 12) group. The experimental group (EG) performed three-dimensional active trunk training exercises using the Space Balance 3D system, while the control group (CG) performed only general trunk training exercises five times per week, for a total of three weeks. The Trunk Impairment Scale (TIS), trunk muscle strength, balance ability using the Space Balance 3D system, and Brunel Balance Assessment (BBA) scores were assessed before and after the intervention. Pre-to-post intervention improvement was noted in all outcome measures for both groups (p< 0.05). Post intervention, the TIS, trunk muscle strength, static balance, and BBA scores were significantly higher in the EG than those in the CG (p< 0.05). Our study suggests that the three-dimensional active trunk training exercise may be more effective compared to the general trunk training exercise in improving trunk control ability, trunk muscle strength, and balance ability in sub-acute stroke patients.


Outcome of Bridge to Lung Transplantation With Extracorporeal Membrane Oxygenation in Pediatric Patients 12 Years and Older.
There is a reluctance to using extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation in the pediatric population. Pediatric patients between ages 12 and 18 years are eligible for acuity-based lung transplantation using the Lung Allocation Score and may be suitable for adult allografts, increasing the donor pool and thus leading to a successful bridge to lung transplantation. The United Network for Organ Sharing dataset was queried for primary lung transplantation in pediatric patients (12-18 years) from 2005 to 2016. Groups were divided into those who were on ECMO (bridged [BG]) and not on ECMO (nonbridged [NBG]) at the time of listing for lung transplant. The groups comprised 16 BG and 375 NBG patients. Fourteen BG patients (88%) survived the first 30 days. One-year (83.3% vs 86.2%, P = .78) and 3-year (66.7% vs 55.1%, P = .57) survivals were similar in the BG and NBG groups, respectively. Donors in the BG group were more likely to be adults. The median wait-list times were shorter (10.5 [interquartile range {IQR}, 11] vs 93 [IQR, 221] days, P < .001), with a higher Lung Allocation Score (89.8 vs 36.6, P < .001) and similar median ischemic times (5.19 [IQR, 2.32] vs 5.34 [IQR, 1.92] hours, P = .85) in the BG group compared with the NBG group. The median post-transplant length of stay was longer in the BG group (33 [IQR, 31] vs 17 [IQR, 12] days, P = .007) and was the only factor predictive of 3-year mortality. Longer wait-list time had a higher mortality in the BG group. ECMO as a bridge to lung transplantation is a reasonable strategy in pediatric patients aged ≥ 12 years with acceptable operative mortality and similar 1- and 3-year survival compared with nonbridged patients despite higher acuity. Bridged patients were more likely to receive adult donor lungs.


Sunitinib versus pazopanib for patients with metastatic renal cell carcinoma: 2 Turkish hospital experience.
Sunitinib (SUN) and pazopanib (PAZ) are 2 oral tyrosine kinase inhibitors against vascular endothelial growth factor. Their efficacy and safety in metastatic renal cell carcinoma has been proven with phase iii studies. However, real world data is limited. The objective of this study is to assess the clinical benefit of SUN and PAZ in routine practice. We reviewed the medical records of 79 metastatic renal cell carcinoma patients treated with SUN (50mg/day on 4/2-schedule) or PAZ (800mg/day continuously). Patients were assessed retrospectively at 2 Turkish hospitals between 2006 and 2016. For the entire cohort median age of patients was 60 (28-87) years and 70% of them were male. The objective response rate and disease control rate in SUN/PAZ groups were 34/37% (P=.96) and 78/87% (P=.046), respectively. With a median follow up duration of 15 months, median progression-free survival and overall survival in SUN/PAZ groups were 8/8 months (P=.83) and 22/21 months (P=.53), respectively. The common all grade toxicities for SUN vs. PAZ were fatigue (59 vs. 74%), skin changes (44 vs. 44%), anemia (35 vs. 42%), hypothyroidism (37 vs. 19%; P=.02) and hypertension (33 vs. 50%). In patients treated with SUN, total grade 3-4 toxicities (mean number of toxic events per patients) were 0.71, whereas in patients treated with PAZ, total grade 3-4 toxicities were 0.11 (P<.001). SUN was associated with an increased incidence of grade 3-4 fatigue (P=.007), anemia (P=.001) and hypothyroidism that needed therapy (P=.02). Dose reduction in 49 and 24% of patients (P=.02), and treatment cessation in 37 and 26% of patients (P=.37) were required in the SUN and PAZ groups, respectively. In our study, there was no difference in terms of survival outcomes between 2 agents. However, patients treated with SUN had more grade 3-4 adverse events which prompted dose reduction.


Iatrogenic prematurity due to elective termination of the uncomplicated pregnancy: a major perinatal health care problem.
In a series of 1,000 newborn infants referred to a regional neonatal center, 32 iatrogenically preterm infants were identified. All had been delivered following elective termination of uncomplicated, apparently term pregnancies, without prior documentation of fetal lung maturity or ultrasonic determination of fetal biparietal diameter. Associated acute morbidity included asphyxia neonatorum in 10, respiratory distress syndrome in 24, and pneumothorax or pneumomediastinum in nine patients. One infant died. Hospital costs totaled $150,643, for a mean of $4,701 per patient. The unexpected premature births were associated with major parental grief reactions and alterations in their daily activities, Iatrogenic prematurity is a major regional health care problem which, when viewed on a national basis, may affect thousands of newborn infants and their families annually. Our data suggest the need for more accurate assessment of fetal maturity, before elective termination of pregnancy, by well-established techniques.


Intraoperative neurophysiologic monitoring in spine surgery. Developments and state of the art in France in 2011.
Intraoperative spinal cord monitoring consists in a subcontinuous evaluation of spinal cord sensory-motor functions and allows the reduction the incidence of neurological complications resulting from spinal surgery. A combination of techniques is used: somatosensory evoked potentials (SSEP), motor evoked potentials (MEP), neurogenic motor evoked potentials (NMEP), D waves, and pedicular screw testing. In absence of intraoperative neurophysiological testing, the intraoperative wake-up test is a true form of monitoring even if its latency long and its precision variable. A 2011 survey of 117 French spinal surgeons showed that only 36% had neurophysiological monitoring available (public healthcare facilities, 42%; private facilities, 27%). Monitoring can be performed by a neurophysiologist in the operating room, remotely using a network, or directly by the surgeon. Intraoperative alerts allow real-time diagnosis of impending neurological injury. Use of spinal electrodes, moved along the medullary canal, can determine the lesion level (NMEP, D waves). The response to a monitoring alert should take into account the phase of the surgical intervention and does not systematically lead to interruption of the intervention. Multimodal intraoperative monitoring, in presence of a neurophysiologist, in collaboration with the anesthesiologist, is the most reliable technique available. However, no monitoring technique can predict a delayed-onset paraplegia that appears after the end of surgery. In cases of preexisting neurological deficit, monitoring contributes little. Monitoring of the L1-L4 spinal roots also shows low reliability. Therefore, monitoring has no indication in discal and degenerative surgery of the spinal surgery. However, testing pedicular screws can be useful. All in all, thoracic and thoracolumbar vertebral deviations, with normal preoperative neurological examination are currently the essential indication for spinal cord monitoring. Its absence in this indication is a lost opportunity for the patient. If neurophysiological means are not available, intraoperative wake-up test is a minimal obligation.


Donor Killer Immunoglobulin-Like Receptor Profile Bx1 Imparts a Negative Effect and Centromeric B-Specific Gene Motifs Render a Positive Effect on Standard-Risk Acute Myeloid Leukemia/Myelodysplastic Syndrome Patient Survival after Unrelated Donor Hematopoietic Stem Cell Transplantation.
Donor killer immunoglobulin-like receptor (KIR) group B profiles (Bx) and homozygous of centromeric motif B (Cen-B/B) are the most preferable KIR gene content motifs for hematopoietic stem cell transplantation (HSCT). The risk of transplant from Bx1 donors and the benefit of the presence of Cen-B (regardless of number) were observed for standard-risk acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) patients in this 4-year retrospective study. A total of 210 Chinese patients who underwent unrelated donor HSCT were investigated. Donor KIR profile Bx was associated with significantly improved overall survival (OS; P = .026) and relapse-free survival (RFS; P = .021) and reduced nonrelapse mortality (NRM; P = .017) in AML/MDS patients. A significantly lower survival rate was observed for transplants from Bx1 donors compared with Bx2, Bx3, and Bx4 donors for patients in first complete remission (n = 82; OS: P = .024; RFS: P = .021). Transplant from donors with Cen-B resulted in improved OS (HR = .256; 95% CI, .084 to .774; P = .016) and RFS (HR = .252; 95% CI, .084 to .758; P = .014) in AML/MDS patients at standard risk. However, this particular effect did not increase with a higher number of Cen-B motifs (cB/B versus cA/B; OS: P = .755; RFS: P = .768). No effect was observed on high-risk AML/MDS, acute lymphoblastic leukemia/non-Hodgkin lymphoma, and chronic myelogenous leukemia patients. Avoiding the selection of HSCT donors of KIR profile Bx1 is strongly advisable for standard-risk AML/MDS patients. The presence of the Cen-B motif rather than its number was more important in donor selection for the Chinese population.


Applications of in vivo and in vitro solid-phase microextraction techniques in plant analysis: A review.
As a very popular sample preparation technique, solid-phase microextraction (SPME) coupled with various analytical instrumentation, has been widely used for the determination of trace levels of different plant compounds, such as volatile organic compounds (VOCs) emitted from the different plant organs, and environmental contaminants in plants. In this review, recent applications of in vitro and in vivo SPME in plant analysis are discussed and summarized according to the different organs of plants, including fruits, flowers, leaves, stems, roots and seeds, and the whole plant as well. Future developments and applications of SPME in plant analysis, especially in vivo sampling approaches, are also prospected.