Cancer stem cells in human digestive tract malignancies.
Digestive tract malignancies, including oral, pharyngeal, esophageal, gastric, and colorectal cancers, are among the top 10 most common cancers worldwide. In spite of using various treatment modalities, cancer patients still suffer from recurrence and metastasis of malignant cells. Cancer stem cells (CSCs) are undifferentiated and highly proliferative malignant cells with unique properties mediated by overexpression of stemness markers, metastasis-related proteins, drug transporters, and DNA repair machinery. Due to their salient characteristics, it has been suggested that CSCs are responsible for tumor initiation, progression, invasion, recurrence, and therapy resistance. Exploring different aspects of CSC biology has fueled a great enthusiasm in designing novel therapeutic strategies to help patients. For instance, identification of markers associated with digestive tract CSCs, such as CD44, CD133, CD24, EpCAM, LGR5, ALDH1, and BMI1, has made it possible to develop more accurate diagnosis approaches. In addition, specifically targeting CSCs by their markers imposes fewer side effects and improves therapeutic outcomes. Here, we focus on the current status of CSC biology in digestive tract cancers, with emphasis on CSC markers, and review achieved progress in eradication of digestive tract CSC cells.


Manitoba to develop Aboriginal AIDS strategy.
Manitoba has embarked on a process to develop a Provincial Aboriginal AIDS Strategy separate from the Provincial AIDS Strategy.


The influence of work intensity on postexercise proteinuria.
Fifteen men were studied during 100 m, 400 m and 3,000 m runs at maximal speed to determine total urinary protein and albumin excretion rates in relation to different distances of running. Venous blood lactate rose to 7.5 mmol.l-1 after the 100 m and 3,000 m events, while reaching 12 mmol.l-1 after the 400 m dash. Total urinary protein excretion increased to 330, 1640 and 565 micrograms.min-1 after the 100 m, 400 m and 3,000 m runs respectively, as compared with basal values (70 micrograms.min-1). In the meantime, albumin excretion increased respectively by 5, 25 and 18 fold of the resting values. The renal clearance of albumin increased to 0.84, 5.62 and 3.35 microliter.min-1 after the three runs, as compared with a mean value of 0.19 microliter.min-1 at rest. Exponential relationships (r = 0.85) were recorded between post-exercise venous lactate and albumin, and total protein excretion. The present work illustrates the major influence of the intensity of exercise (anaerobic glycolytic component), rather than its duration, on the excretion rate of urinary proteins.


Treatment plan and summary templates: the experience of one practice.
Using a formal treatment plan template enables clearer and more fruitful discussions between physician and patient and among physicians within a practice. Treatment plans are vital to formal chemotherapy teaching sessions for patients beginning therapy, regardless of disease histology or treatment intent.


Radial artery cannulation guided by Doppler ultrasound.
A technique to enhance difficult percutaneous radial artery cannulations using Doppler ultrasound is described. A series of 12 patients (nine hypotensive and three normotensive patients with poorly palpable or absent radial pulses) was assembled and the radial arteries were cannulated using standard intravenous catheters and a hand-held Doppler ultrasound device. Localization and cannulation of the arteries was facilitated by noting the characteristic sounds using the Doppler. Eleven of the 12 patients had successful cannulation of the radial artery. In one case the artery was localized but the catheter could not be advanced. No complications were encountered. It was concluded that the use of a common Doppler ultrasound on selected patients with poor peripheral pulses may facilitate percutaneous radial artery cannulations and minimize the number of catheter punctures before successful placement.


Fifty years integrating neurobiology and psychology to study attention.
At the time of the start of Biological Psychology cognitive studies had developed approaches to measuring cognitive processes. However, linking these to the underlying biology in the typical human brain had hardly begun. A critical step came in 1988 when methods for imaging the human brain in cognitive tasks began. By 1990 it was possible to describe three brain networks that carried out the hypothesized cognitive functions outlined 20 years before. Their development was traced in infancy, first using age-appropriate tasks and later through resting state imaging. Imaging was applied to both voluntary and involuntary cued shifts of visual orienting in humans and primates, and a summary was presented in 2002. By 2008 these new imaging findings were used to test hypotheses about the genes involved in each network. Recently, studies of mice using optogenetics to control populations of neurons have brought us closer to a synthesis of how attention and memory networks operate together in human learning. Perhaps the coming years will bring us to an integrated theory of aspects of attention using data from all the levels that can illuminate these issues, thus fulfilling a key goal of the Journal.


Burn healing in organ cultures of embryonic chicken skin: a model system.
Burn wounds cause complex damage to the skin. Unlike simple cuts, burns cause a graded damage at the margin of the wound and leave biochemically complex debris in the wound, two factors that complicate the process of wound healing. To develop an in vitro system for studying cellular responses to burns in whole tissue, we have applied a standardized burn wound to organ cultures of embryonic chicken skin and evaluated cellular changes in response to the burn damage. This simplified system is not subject to uncontrolled infection and does not involve angiogenesis and granulation. Thus, these cultures provide a simplified model of how cells of the dermis and epidermis in and around a burn wound respond to heat damage early in the process of healing.


Surface interaction between glycosaminoglycans and calcium oxalate.
Molecules and macromolecules are known to alter the process of crystallization, either through inhibition or promotion of nucleation, growth, and/or aggregation. One particular group of macromolecules, glycosaminoglycans (GAGs), has been of interest in our laboratory. The GAGs chondroitin A, chondroitin C, heparan sulfate, dermatan sulfate, hyaluronic acid, and keratan sulfate have all been shown to be inhibitors of calcium oxalate crystallization. Heparin, the only GAG which is not naturally present in urine, is the most potent inhibitor of all GAGs. Using the method of Langmuir isotherm adsorption, we studied the adsorption of certain GAGs onto calcium oxalate crystals. Under standardized conditions, heparin, chondroitin C, hyaluronic acid, and pentosan polysulfate (a synthetic polyanionic molecule similar to, but a weaker inhibitor than, heparin) were adsorbed onto calcium oxalate. The total amount of GAG required to maximally cover the crystal surface, as well as the equilibrium concentration at which surface was half-covered with GAG (inversely related to the desorption energy) were measured. Chondroitin C was adsorbed in the greatest amount, followed by heparin, pentosan polysulfate, and finally hyaluronic acid. Using the method of fiducial limits, the only insignificant difference was between heparin and chondroitin C, and between hyaluronic acid and pentosan polysulfate. Pentosan polysulfate required significantly higher equilibrium concentration than heparin and hyaluronic acid to cover half of the surface of the calcium oxalate crystals. The principle of Langmuir isotherm adsorption can be useful in predicting the effects of macromolecules on crystallization. Weaker inhibitors bind with less affinity than do stronger inhibitors. Further work is underway to characterize other inhibitors and promoters.


Clinical Features of Endogenous Endophthalmitis Secondary to Minimally Invasive Upper Urinary Tract Calculus Removal.
To evaluate endogenous endophthalmitis clinical features following minimally invasive removal of upper urinary tract calculi. Medical records of twelve patients (17 eyes) with endogenous endophthalmitis secondary to minimally invasive upper urinary tract calculus removal were retrospectively reviewed. Diabetes mellitus was found in 7 patients (58%). 10 patients (83%) suffered from fever. The stone extraction and ocular symptom onset interval ranged from 2 to 22 days. All eyes presented as vitritis and fluffy yellow-white retinal exudates. Hypopyon was only found in 3 eyes (18%). 5 patients (42%) were misdiagnosed as uveitis which led to mismanagement. Ocular fluids were culture positive for only C. albicans in 12 eyes (71%). 10 of 12 eyes (83%) with silicon oil tamponade obtained a final BCVA≥0.05. C. albicans was the most common endogenous endophthalmitis pathogen after urinary calculus removal by minimally invasive surgery. Pars plana vitrectomy with silicon oil tamponade may be helpful to achieve a favorable visual outcome. Routine ophthalmologic evaluation by the uveitis or vitreoretinal specialist may be necessary within 2 weeks after the urological procedures.


Neutral functional realignment orthosis prevents hand pain in patients with subacute stroke: a randomized trial.
To quantify the preventive effect of a neutral functional realignment orthosis on pain, mobility, and edema of the hand in subacute hemiparetic poststroke patients with severe motor deficits. Randomized trial. Rehabilitation center. Poststroke patients (N=30) with subacute hemiparesis and severe deficits of the upper limb were enrolled. Fifteen patients were randomized to a standard rehabilitation program without orthosis and 15 patients received an experimental orthosis in addition to their standard rehabilitation program. The orthosis group wore the neutral functional realignment orthosis for at least 6 hours daily. Hand pain at rest (visual analog scale), wrist range of motion (Fugl-Meyer Assessment subscale), and edema of hand and wrist (circumferences). Outcome measures were assessed at time of randomization and after 13 weeks between groups. At baseline, 2 patients in each group complained about a painful hand. After 13 weeks, 8 subjects in the control group and 1 subject in the orthosis group complained of hand pain (P=.004). Mobility and edema evolved similarly in both groups. Neutral functional realignment orthoses have a preventive effect on poststroke hand pain, but not on mobility and edema in the subacute phase of recovery.


Tongue features of patients with coronavirus disease 2019: a retrospective cross-sectional study.
Traditional Chinese medicine (TCM) has been widely used in the treatment of coronavirus disease 2019 (COVID-19). Tongue features should be referred for diagnosis and treatment of diseases in TCM. Therefore, it is necessary to analyze the tongue features of the patients suffered from COVID-19. COVID-19 Symptom Database (established by Evidence-based Medicine Center of Tianjin University of TCM) was searched for eligible tongue pictures. The tongue pictures were assessed by TCM experts to extract the data of tongue color, coating color, tongue body shape and coating proper feature. The relationship between tongue features and patient's condition was analyzed. Patients diagnosed as mild and moderate COVID-19 commonly had light red tongue and white coating. Severe patients had purple tongue and yellow coating. The proportion of critical patients with tender tongue increased to 75%. Greasy coating was a significant characteristic of patients with COVID-19. The proportions of greasy coating were 53.33%, 73.30%, 83.67 and 87.5% in disease category of mild, moderate, severe and critical. In addition, the thick coating proportion increased from mild (24.89%) to critical (50.00%). Tongue features have certain relationship with the category of COVID-19. Tongue features can serve as potential indicators for the evaluation of patient's condition and prognosis. Further studies are needed to enhance the quantification of tongue features and develop standards.


The development of opiate tolerance may dissociate from dependence.
Experiments on opiate sensitive peripheral tissue preparations such as the mouse vas deferens and the guinea-pig ileum have demonstrated the ability to induce very high degrees of selective tolerance towards particular opiate agonists. Interestingly, the highly tolerant mouse vas deferens failed to display any sign of dependence as judged by the inability of naloxone to precipitate a withdrawal sign. In analogy, the present studies on the guinea-pig ileum revealed a striking dissociation in the degree of tolerance and dependence developed. Opiate receptor binding studies on both tissues point to distinct differences in the opiate-induced effector mechanisms. It is concluded that adaptational changes upon chronic opiate receptor activation may occur at multiple sites within the effector system of the opiate receptor.


Stimulation of gastric inhibitory polypeptide in normal and duodenal ulcer patients.
To investigate the role of gastric inhibitory polypeptide (GIP), a potent inhibitor of gastric acid secretion, in the hypersecretion associated with duodenal ulcer, we compared the serum GIP concentrations in 11 healthy subjects and 16 duodenal ulcer patients after the stimulation of GIP release by a mixed meal. Fasting and postprandial serum gastrin and GIP concentrations were measured by radioimmunoassay at frequent intervals after the ingestion of a test meal. The duodenal ulcer patients showed an augmented and significantly greater release of GIP as well as of gastrin compared to normal subjects. These results indicate that a defective GIP release cannot account for the gastric hypersecretion seen in patients with duodenal ulcer. The mechanism of the increased GIP response in patients with duodenal ulcer is not clear from these studies.


Prolactin-regulated apoptosis of Nb2 lymphoma cells: pim-1, bcl-2, and bax expression.
Lactogen-dependent Nb2 lymphoma cells, widely employed for studying prolactin (PRL) mitogenic mechanisms, are also useful for investigations of apoptosis in T-lineage lymphocytes. Utilizing PRL-dependent Nb2-11 cultures, apoptosis-regulatory genes were evaluated for participation in dexamethasone- (DEX) provoked cell death or its inhibition by PRL. Treatment of lactogen-starved, G1-arrested Nb2-11 cells with DEX (100 nM) activated apoptosis within 12 h evaluated by flow cytometric analysis of fragmented DNA. This effect was not associated with altered expression of bcl-2, bax, or pim-1. PRL (10 ng/mL), coincubated with DEX-treated cells, completely blocked DEX-induced apoptosis. This inhibition was associated with increased expression of bcl-2 and pim-1 mRNAs, genes reported to suppress apoptosis, within 2-6 h after addition of the hormone. Moreover, the increased transcription of bcl-2 and pim-1 was coupled to increases in their protein levels. The results suggest that bcl-2, bax, and pim-1 do not play a critical role in DEX-induced apoptosis in Nb2 cells. However, expression of bcl-2, together with pim-1, may have a role in mediating the antiapoptotic actions of PRL.


Antiradical effects in L-propionyl carnitine protection of the heart against ischemia-reperfusion injury: the possible role of iron chelation.
L-Propionyl carnitine has been shown to improve the heart's mechanical recovery and other metabolic parameters after ischemia-reperfusion. However, the mechanism of protection is unknown. The two dominating hypotheses are: (i) L-propionyl carnitine can serve as an energy source for heart muscle cells by being enzymatically converted to propionyl-CoA and subsequently utilized in the Krebs cycle (a metabolic hypothesis), and (ii) it can act as an antiradical agent, protecting myocardial cells from oxidative damage (a free radical hypothesis). To test the two possible pathways, we compared the protection afforded to the ischemia-reperfused hearts by L-propionyl carnitine and its optical isomer, D-propionyl carnitine. The latter cannot be enzymatically utilized as an energy source. The Langendorff perfusion technique was used and the hearts were subjected to 40 min of ischemia and 20 min of reperfusion. In analysis of ischemia-reperfused hearts, a strong correlation was found between the recovery of mechanical function and the presence of protein oxidation products (protein carbonyls). Both propionyl carnitines efficiently prevented protein oxidation but L-propionyl carnitine-perfused hearts had two times greater left ventricular developed pressure. The results indicate that both metabolic and antiradical pathway are involved in the protective mechanism of L-propionyl carnitine. To obtain a better insight of the antiradical mechanism of L-propionyl carnitine, we compared the ability of L- and D-propionyl carnitines, L-carnitine, and deferoxamine to interact with: (i) peroxyl radicals, (ii) oxygen radicals, and (iii) iron. We found that none of the carnitine derivatives were able to scavenge peroxyl radicals or superoxide radicals. L- and D-propionyl carnitine and deferoxamine (not L-carnitine) suppressed hydroxyl radical production in the Fenton system, probably by chelating the iron required for the generation of hydroxyl radicals. We suggest that L-propionyl carnitine protects the heart by a dual mechanism: it is an efficient fuel source and an antiradical agent.


Corticospinal properties are associated with sensorimotor performance in action video game players.
Notwithstanding the apparent demands regarding fine motor skills that are required to perform in action video games, the motor nervous system of players has not been studied systematically. In the present study, we hypothesized to find differences in sensorimotor performance and corticospinal characteristics between action video game players (Players) and Controls. We tested sensorimotor performance in video games tasks and used transcranial magnetic stimulation (TMS) to measure motor map, input-output (IO) and short intra-cortical inhibition (SICI) curves in the first dorsal interosseous (FDI) muscle of Players (n = 18) and Control (n = 18). Players scored higher in performance tests and had stronger SICI and higher motor evoked potential (MEP) amplitudes. Multiple linear regressions showed that Players and Control differed with respect to their relation between reaction time and corticospinal excitability. However, we did not find different motor map topography or different IO curves for Players when compared to Controls. Action video game players showed an increased efficiency of motor cortical inhibitory and excitatory neural networks. Players also showed a different relation of MEPs with reaction time. The present study demonstrates the potential of action video game players as an ideal population to study the mechanisms underlying visuomotor performance and sensorimotor learning.


The contribution of stereo vision to the control of braking.
In this study the contribution of stereo vision to the control of braking in front of a stationary target vehicle was investigated. Participants with normal (StereoN) and weak (StereoW) stereo vision drove a go-cart along a linear track towards a stationary vehicle. They could start braking from a distance of 4, 7, or 10m from the vehicle. Deceleration patterns were measured by means of a laser. A lack of stereo vision was associated with an earlier onset of braking, but the duration of the braking manoeuvre was similar. During the deceleration, the time of peak deceleration occurred earlier in drivers with weak stereo vision. Stopping distance was greater in those lacking in stereo vision. A lack of stereo vision was associated with a more prudent brake behaviour, in which the driver took into account a larger safety margin. This compensation might be caused either by an unconscious adaptation of the human perceptuo-motor system, or by a systematic underestimation of distance remaining due to the lack of stereo vision. In general, a lack of stereo vision did not seem to increase the risk of rear-end collisions.


Computer analysis of cardiovascular parameters.
A computer program is described for the analysis of several cardiovascular parameters frequently measured or derived in the chronically instrumented dog model. Data are stored on magnetic tape and are subsequently analyzed with the Apple IIe microcomputer equipped with the ADALAB (Interactive Microware, Inc.) analog-to-digital convertor. Not limited to the chronically instrumented animal model, the program is capable of analyzing left ventricular pressure, three channels of regional myocardial segment length, coronary flow velocity as measured by the Doppler ultrasonic flow technique, and two channels of systemic arterial pressure. Derived data include: left ventricular dP/dtmax, left ventricular pressure-heart rate product, left ventricular ejection time, tension time index; percent segment length shortening and velocity of shortening, dL/dt(s)max, regional stroke work and power, duration of systole and diastole; mean coronary flow velocity, peak diastolic and systolic flow velocity, and true mean systemic arterial pressure.


Amino acids as stabilizers for spray-dried simvastatin powder for inhalation.
The use of amino acids as excipients is a promising approach to improve the physical stability and powder dispersibility of spray-dried powders for inhalation. The aim of this study was to investigate the stabilizing effect of different amino acids on spray-dried amorphous powders for inhalation using simvastatin (SV) as a model compound. Two hydrophobic amino acids (leucine, LEU and tryptophan, TRP), and one hydrophilic amino acid (lysine, LYS) were spray dried from 1% (w/v) solutions with SV at a molar ratio of 1:1 into dry powders for inhalation. Scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) were used to characterize the morphology, solid form and potential intermolecular interactions of the spray-dried powders. X-ray photoelectron spectroscopy (XPS) was used to analyse the chemical composition of the surface of the particles. The physical stability of the dry powders was examined upon storage in controlled conditions. A Next generation impactor (NGI) was applied to assess the in vitro aerosol performance of the powders. XRPD and DSC results confirmed that the spray-dried SV-LEU was composed of crystalline LEU and amorphous SV, the spray-dried SV-LYS was co-amorphous, and the spray-dried SV-TRP was an amorphous system with two phases. XPS analyses revealed that the surface of the spray-dried SV-LEU particles were LEU rich, indicating surface-enrichment of LEU in these particles. In contrast, an almost even distribution of TRP and SV at the surface of spray-dried SV-TRP was observed. FTIR results indicated no intermolecular interaction between SV and the amino acids used in the present study. The three spray-dried samples were physically stable after eight months storage in a desiccator (12% RH, ca. 22 °C). Nevertheless, spray-dried SV-LEU exhibited the best storage stability as compared to the other two spray-dried samples when the samples were stored at 60% RH, 25 °C. Both, the spray-dried SV-LEU and SV-TRP exhibited higher fine particle fractions than the spray-dried SV-LYS. Both the spray-dried SV-LEU and SV-TRP exhibited better aerosol performance and storage stability compared to the spray-dried SV-LYS. Compared to TRP, LEU exhibited better protection of spray-dried amorphous SV from re-crystallization, which could be attributed to the formation of a LEU crystalline shell covering SV upon the spray drying process.


Exhaustive electromembrane extraction of some basic drugs from human plasma followed by liquid chromatography-mass spectrometry.
Citalopram, loperamide, methadone, paroxetine, pethidine, and sertraline were extracted exhaustively with electromembrane extraction (EME) by increasing the number of hollow fibers from one to three. Experiments reported recoveries in the range 97-115% from 1000μl spiked water samples. EME was accomplished with 200V as extraction voltage, the extraction time was set to 10min (equilibrium), and the extraction unit was subjected to 1200 revolutions per minute (rpm). The same experiment with different geometry in a stagnant system conducted with 21μl acceptor solution provided recoveries from 50μl undiluted human plasma (pH 7.4) in the range of 56-102% for the six basic model substances. In each experiment the acceptor solution was distributed into three separately hollow fibers in the same sample vial. The importance of an electrical field was verified by comparing EME with liquid-phase microextraction (LPME) under optimal conditions and demonstrated that the time needed to reach equilibrium was reduced by EME. EME-LC/MS provided linearity >0.99 (r(2) values) for the six basic model substances, and the repeatability within the low therapeutic range (10ng/ml) was in the range 5.1-21.4% RSD. LC-MS provided estimated limit of quantification (S/N=10) in the range 0.6-3.2ng/ml. Eventually, patient samples from a reference laboratory were analyzed and provided reliable results with a relative difference <14% compared to stated values from the reference laboratory.


Corneal endothelial damage after simultaneous PRK and corneal cross-linking in stable keratoconus.
To describe a case of endothelial damage after photorefractive keratectomy (PRK) combined with corneal cross-linking (CXL). A 34-year-old man with diagnosis of stable keratoconus presented at our clinic complaining of vision loss in the left eye after same-day simultaneous PRK and CXL. One year postoperatively, slit-lamp examination showed central corneal haze and specular microscopy demonstrated reduced endothelial cell density compared with the preoperative state. Corrected distance visual acuity decreased from 18/20 preoperatively to 20/60 postoperatively. The thinnest corneal thickness value decreased from 432 μm preoperatively to 328 μm postoperatively. The present case demonstrates the importance of appropriate determination of treatment parameters for simultaneous PRK and CXL in keratoconus, even if the disease is stable prior to treatment.


Magnetic resonance imaging in detection and functional assessment of coronary artery disease.
The past few years have brought significant improvements in the field of cardiovascular magnetic resonance imaging (MRI), which evolved from an experimental technique to a clinically accepted method of coronary artery disease detection (stress MRI) and viability assessment. In this article, we describe current MRI technology for detection and functional assessment of ischemia, such as dobutamine/atropine MRI, perfusion techniques, viability, and flow reserve in native coronary arteries and grafts. With further refinement in the technology, wide acceptance of cardiovascular MRI is anticipated in clinical practice.


[Effects of NaBT and NSAIDs on colorectal adenoma-carcinoma cells].
We investigated the primary adenoma cells and HT-29 cells in an attempt to know whether NaBT and two NSAIDs (aspirin and NS-398) could be used as effective adjuvant for reducing cell proliferation, and to explore the possible mechanisms therein involved. MTT was employed in detecting the anti-proliferative effects on both adenoma and HT-29 culture cells. Both butyrate and NSAIDs could inhibit the proliferation of cells. The effects of the NSAIDs could be synergistically strengthened by combining with butyrate. NaBT and the two NSAIDs could inhibit the cell proliferation when used separately, and a combination of butyrate with aspirin or NS-398 could enhance the inhibitory effects.


Alteration of cell cycle regulators correlates with survival in epithelial ovarian cancer patients.
The p16-cyclinD1/CDK4-pRb pathway (RB pathway) and p14ARF-MDM2-p53 pathway (p53 pathway) work at the G1-S checkpoint, and the ATM-chk2-CDC25-cyclinB1/cdk1 pathway works at the G2-M checkpoint. The disruption of these pathways is thought to be related to the prognosis of human cancer. In this study, we analyzed the status of these pathways in 107 epithelial ovarian cancer (EOC) patients by immunohistochemistry and evaluated the relationship of these results with chemotherapy response and the prognosis. Altered RB, p53, and G2 pathways were detected in 50.5% (54/107), 51.4% (55/107), and 33.6% (36/107) of cases, respectively. The overall survival (OS) of 77.3% for patients with a normal RB pathway was significantly higher than the OS of 50.0% for patients with an altered RB pathway (by Kaplan-Meier analysis, P = 0.0021). The OS of 66.2% for patients with a normal G2 pathway was significantly higher than the OS of 58.3% for patients with an altered G2 pathway (P = 0.0416). However, the status of the p53 pathway was not related to OS. By univariate and multivariate analyses, advanced stage, high histological grade, altered RB pathway, and altered G2 pathway were significant predictors of poor OS. However, there was no significant relationship between pathway status and chemotherapy response. The status of the RB pathway and of the G2 pathway were independent prognostic factors of EOC.


Analysis of Quality of Life Subjective Perception by Patients Treated for Prostate Cancer with the EORTC QLQ-C30 Questionnaire and QLQ-PR25 Module.
Prostate cancer in men is the second most occurring cancer in Poland and represents approximately 13.2 % of all cancers. At the same time, it is the third largest cause of death in men, being responsible for approximately 8 % of deaths. The study was conducted among patients of Oncological Hospital in Wieliszew. The study included 83 men diagnosed with prostate cancer at the age of 51-84 years. The patients gave their written consent to participate in the study, to which the overall standardized questionnaires EORTC QLQ-C30 and QLQ-PR25 for patients with prostate cancer was applied. Significant deterioration of the state of health due to cancer was indicated by a total of 10.84 % of patients. At the same time, it was found that although there are differences between quality of life in various age groups of respondents, they are statistically insignificant (Chi2 = 59.96; p = 0.00734; R = 0.09; p > 0.05). Subjective QoL did not depend on the stage of cancer treatment, type of therapy, or significant deterioration in the patient's state of health in the last stage of disease. Both disease and therapy have impact on quality of life in all its dimensions, in particular as regards the patient's physical functioning and his frequent fatigue. There is a strong relationship between a patient's subjective assessment of quality of life and pain that significantly hampers everyday activities. This demonstrates the need for continuous monitoring and relieving pain directly associated with cancer and methods of its treatment.


Twenty-four month comparison of apolipoproteins A-1, A-II and B in contraceptive implant users (Norplant and Implanon) in Birmingham, United Kingdom.
A 2-year prospective, randomized study of 60 implant users was performed to evaluate fasting serial serum apolipoprotein A-I, A-II, and B levels before insertion and every 3 months in users of two contraceptive implants releasing levonorgestrel (Norplant) and 3-ketodesogestrel/etonogestrel (Implanon) in Birmingham, United Kingdom. All changes in serum apolipoprotein concentrations, irrespective of an increase or decrease, were smaller than one standard deviation of the mean concentration at baseline and did not exceed the normal range for the laboratory, thus implying no evidence of an increased risk of coronary heart disease.


Superficial transitional cell carcinoma of the bladder associated with mucosal involvement of the prostatic urethra: results of treatment with intravesical bacillus Calmette-Guerin.
Intravesical Pasteur strain bacillus Calmette-Guerin was used to treat 8 patients with mucosal transitional cell carcinoma of the prostatic urethra associated with superficial transitional cell carcinoma of the bladder. Complete initial response in the prostatic urethra was obtained in 7 of the 8 patients. Two patients had progression of disease during intravesical bacillus Calmette-Guerin therapy (1 in the prostate and 1 in the bladder) and they received further surgical therapy. Of the 6 complete responders 1 patient had invasive ureteral, vesical and prostatic tumor 15 months after bacillus Calmette-Guerin therapy, and he underwent nephroureterectomy and cystoprostatourethrectomy. Two patients required additional transurethral therapy for recurrent superficial tumors in the bladder but they have shown no evidence of recurrence in the prostatic urethra. Three patients have remained free of disease at 8 to 36 months. Before radical cystoprostatourethrectomy and urinary diversion are recommended, our study supports a course of bacillus Calmette-Guerin therapy as initial treatment for patients with superficial transitional cell carcinoma of the bladder associated with mucosal involvement of the prostatic urethra.


An optimised CRISPR/Cas9 protocol to create targeted mutations in homoeologous genes and an efficient genotyping protocol to identify edited events in wheat.
Targeted genome editing using the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system has been applied in a large number of plant species. Using a gene-specific single guide RNA (sgRNA) and the CRISPR/Cas9 system, small editing events such as deletions of few bases can be obtained. However larger deletions are required for some applications. In addition, identification and characterization of edited events can be challenging in plants with complex genomes, such as wheat. In this study, we used the CRISPR/Cas9 system and developed a protocol that yielded high number of large deletions employing a pair of co-expressed sgRNA to target the same gene. The protocol was validated by targeting three genes, TaABCC6, TaNFXL1 and TansLTP9.4 in a wheat protoplast assay. Deletions of sequences located between the two sgRNA in each gene were the most frequent editing events observed for two of the three genes. A comparative assessment of editing frequencies between a codon-optimized Cas9 for expression in algae, crCas9, and a plant codon-optimized Cas9, pcoCas9, showed more consistent results with the vector expressing pcoCas9. Editing of TaNFXL1 by co-expression of sgRNA pair was investigated in transgenic wheat plants. Given the ploidy of bread wheat, a rapid, robust and inexpensive genotyping protocol was also adapted for hexaploid genomes and shown to be a useful tool to identify homoeolog-specific editing events in wheat. Co-expressed pairs of sgRNA targeting single genes in conjunction with the CRISPR/Cas9 system produced large deletions in wheat. In addition, a genotyping protocol to identify editing events in homoeologs of TaNFXL1 was successfully adapted.


Hemangioma of the prostate with retrograde ejaculation - a case report.
Hemangioma of the prostate is rarely reported. We here describe a hemangioma of the prostate in a 31-year-old man. The history, imaging characteristics, treatment and one year follow-up results were well documented. The chief complaint was retrograde ejaculation. A 3.1 cm × 2.9 cm mass in the prostate was detected by ultrasound. Transurethral resection of the prostate (TURP) was performed. Pathological examination revealed the mass was hemangioma. Immunohistochemical study found the tissue was SMA, CD34, CD31 positive, but D2-40 negative. Imaging feature combined with pathological result suggests the diagnosis of hemangioma of the prostate. One year follow-up revealed the patient was infertile. We suggest TURP should be performed to remove the hemangioma. Combined treatment is necessary to resolve the patient's infertility.


Unsupervised immunophenotypic profiling of chronic lymphocytic leukemia.
Proteomics and functional genomics have revolutionized approaches to disease classification. Like proteomics, flow cytometry (FCM) assesses concurrent expression of many proteins, with the advantage of using intact cells that may be differentially selected during analysis. However, FCM has generally been used for incremental marker validation or construction of predictive models based on known patterns, rather than as a tool for unsupervised class discovery. We undertook a retrospective analysis of clinical FCM data to assess the feasibility of a cell-based proteomic approach to FCM by unsupervised cluster analysis. Multicolor FCM data on peripheral blood (PB) and bone marrow (BM) lymphocytes from 140 consecutive patients with B-cell chronic lymphoproliferative disorders (LPDs), including 81 chronic lymphocytic leukemia (CLLs), were studied. Expression was normalized for CD19 totals, and recorded for 10 additional B-cell markers. Data were subjected to hierarchical cluster analysis using complete linkage by Pearson's correlation. Analysis of CLL in PB samples (n = 63) discovered three major clusters. One cluster (14 patients) was skewed toward "atypical" CLL and was characterized by high CD20, CD22, FMC7, and light chain, and low CD23. The remaining two clusters consisted almost entirely (48/49) of cases recorded as typical BCLL. The smaller "typical" BCLL cluster differed from the larger cluster by high CD38 (P = 0.001), low CD20 (P = 0.001), and low CD23 (P = 0.016). These two typical BCLL clusters showed a trend toward a difference in survival (P = 0.1090). Statistically significant cluster stability was demonstrated by expanding the dataset to include BM samples, and by using a method of random sampling with replacement. This study supports the concept that unsupervised immunophenotypic profiling of FCM data can yield reproducible subtypes of lymphoma/chronic leukemia. Expanded studies are warranted in the use of FCM as an unsupervised class discovery tool, akin to other proteomic methods, rather than as a validation tool.


A histological and ultrastructural study of wound healing after vomer resection in the beagle dog.
Trauma to the vomer during cleft-palate surgery may impair anterior-posterior growth of the premaxilla and maxilla. The vomer was resected via a palatal flap in four 42-day-old beagle pups; four unoperated dogs served as controls. One experimental and one control animal was perfused at 2, 4, 8 and 12 weeks after surgery and specimens from the vomer-premaxillary suture and from the vomer at the level of the mid-palate were processed for light and electron microscopy. Measurements of maxillary casts showed retardation in anterior-posterior growth and development of an anterior cross-bite in all but one of the experimental animals. Microscopic examination of the healing wound showed granulation tissue and contractile fibroblasts, which were more numerous at the premaxilla-vomer suture than at the posterior site. Developing elastic fibres were also seen. Quantitation of fibroblasts revealed that 25-50 per cent in the control suture had the characteristics of contractile cells, but this reached 75 per cent in the resected group. These cells together with the elastin many constitute a system that retards anterior-posterior growth and leads to cross-bite.


Correction to: Comorbidity in gout at the time of first diagnosis: sex differences that may have implications for dosing of urate lowering therapy.
Unfortunately, after publication of this article [1], it was noticed that Fig. 2 is incorrect.


Effects of uneven elastic loads on breathing pattern of anesthetized and conscious men.
In anesthetized subjects rib cage strapping (RCS) did not change tidal volume (VT) and increased ventilation (V), whereas abdomen strapping (AS) markedly decreased VT and V. Both kinds of strapping decreased expiratory duration (TE), but did not change inspiratory duration (TI) and breathing rate. RCS and AS decreased lung volume by about 200 ml and increased the elastance of the repiratory system by 12 cm H2O/1 and 9 CM H20/l, repectively. The changes produced are mainly due to mechanical factors, although reflexes also seem to be operating in some cases. In conscious subjects RCS decreased VT, TI, TE and did not change V, whereas AS did not change these parameters. The different changes in conscious and anesthetized subjects show the effects of cortical influences, which also partly explain the differen effects elicited in conscious subjects by RCS and AS. The effects produced by RCS are mainly due to the sensation of hindrance to rib cage expansion, rather than to that of rib cage squeezing, as shown by experiments of RCS without reduction of rib cage volume.


Spatial correlation of covid-19 with intensive care unit beds in Paraná.
To analyze the spatial correlation between confirmed cases of covid-19 and the intensive care unit beds exclusive to the disease in municipalities of Paraná. This is an epidemiological study of ecological type which used data from the Epidemiological Report provided by the Department of Health of Paraná on the confirmed cases of covid-19 from March 12, 2020, to January 18, 2021. The number of intensive care beds exclusive to covid-19 in each municipality of Paraná was obtained by the Cadastro Nacional de Estabelecimentos de Saúde (CNES - National Registry of Health Establishments), provided online by the Departamento de Informática do Sistema Único de Saúde (Datasus - Informatics Department of the Brazilian Unified Health System). The Bivariate Moran's Index (local and global) was used to analyze the intensive care bed variable and spatial correlation, with a 5% significance level. LISA Map was used to identify critical and transition areas. In the analyzed period, we found 499,777 confirmed cases of covid-19 and 1,029 intensive care beds exclusive to the disease in Paraná. We identified a positive spatial autocorrelation between the confirmed cases of covid-19 (0.404-p ≤ 0.001) and intensive care beds exclusive to the disease (0.085-p ≤ 0.001) and disparities between the regions of Paraná. Spatial analysis indicated that confirmed cases of covid-19 are related to the distribution of intensive care beds exclusive to the disease in Paraná, allowing us to find priority areas of care in the state regarding the dissemination and control of the disease.


Repeated transmission of X-linked ocular albinism type 1 by a carrier oocyte donor.
To report the transmission of unsuspected X-linked ocular albinism in an oocyte donor program. Case report. University medical center. A 24-year-old white female oocyte donor and the outcomes of three recipient pregnancies. Clinical assessment and molecular diagnostic tests. Mutation detection. Demonstration of carrier status and multiple transmissions of a mutant allele. We describe the transmission of a mutant allele for X-linked ocular albinism from an unsuspected carrier female oocyte donor to three independent pregnancies. We emphasize the need for diligent inquisition to clarify any unusual history of ocular or constitutional signs that might signify an X-linked disorder.


Randomized comparison of effects of two different remifentanil dose on surgical conditions during endoscopic sinus surgery.
The combination of propofol and remifentanil results in better surgical field conditions during endoscopic sinus surgery than inhalation anesthesia. This study compared surgical field conditions between two groups receiving low or high concentration of remifentanil and hemodynamic variables using non-invasive cardiac monitoring. Fifty-four patients between ASA I or II, were randomly assigned to either the high-concentration remifentanil group (HR), effect-site concentration of 8 ng/mL or the low-concentration remifentanil group(LR), effect-site concentration of 4 ng/mL. Surgical condition was evaluated using the Boezaart Surgical Field Grading Scale presented by Boezaart. Cardiac output was measured using non-invasive cardiac monitoring (CSN-1901). In terms of surgical conditions, the HR group showed significantly lower values than the LR group (p = 0.021) at 90 min after the start of surgery. Heart rate was significantly lower in the HR group than the LR group at 30, 60, and 90 min after the start of surgery (30 min; p = 0.005, 60 min; p = 0.002, 90 min; p = 0.001). There was a statistically significant decrease of cardiac output in the HR group compared to the LR group immediately after endotracheal intubation and at 30, 60, and 90 min after the start of surgery (Base; P = 0.222, Intubation; P = 0.016, 30 min; p = 0.014, 60 min; P = 0.012, 90 min; P = 0.008). However, in the case of stroke volume, there was no significant difference between the two groups in all measurements. When comparing the HR group and the LR group, the surgical condition was improved at 90 min after the start of surgery. MAP was lower in the HR group and this was a result of reduction in cardiac output primarily attributed to the decrease in heart rate rather than a decrease in stroke volume. Clinical Trial Registry of the Republic of Korea (KCT0006453).


Effect of Di-(2-ethylhexyl) phthalate (DEHP) on chemical constituents and enzymatic activity of rat liver.
Effect of Di(2-ethylhexyl) phthalate (DEHP), was investigated on chemical constituents and activity of certain enzymes of rat liver. A significant increase in liver weight; total and relative to body weight; decrease in total, free and esterified cholesterol; and no change in dry weight, moisture; RNA, DNA, total lipids, phospholipids, pyruvic acid and lactic acid contents was observed in liver of DEHP-treated rats as compared to controls. Activity of 3 mitochondrial enzymes, malic dehydrogenase, cytochrome-c-oxidase and diaphorase were significantly decreased while that of NADH-cytochrome c reductase, RNAase and DNAase remained unaltered upon treatment. The results suggest that DEHP exerts its hepatotoxic effects by interfering with bioenergetics of the cell.


Re-resection in Incidental Gallbladder Cancer: Survival and the Incidence of Residual Disease.
Re-resection for incidental gallbladder cancer (iGBC) is associated with improved survival but little is known about residual disease (RD) and prognostic factors. In this study, survival after re-resection, RD, and prognostic factors are analyzed. Patients with iGBC were identified from the Netherlands Cancer Registry, and pathology reports of re-resected patients were reviewed. Survival and prognostic factors were analyzed. Overall, 463 patients were included; 24% (n = 110) underwent re-resection after a median interval of 66 days. RD was present in 35% of patients and was most frequently found in the lymph nodes (23%). R0 resection was achieved in 93 patients (92%). Median overall survival (OS) of patients without re-resection was 13.7 (95% confidence interval [CI] 11.6-15.6), compared with 52.6 months (95% CI 36.3-68.8) in re-resected patients (p < 0.001). After re-resection, median OS was superior in patients without RD versus patients with RD (not reached vs. 23.1 months; p < 0.001). In patients who underwent re-resection, RD in the liver (hazard ratio [HR] 5.54; p < 0.001) and lymph nodes (HR 2.35; p = 0.005) were the only significant prognostic factors in multivariable analysis. Predictive factors for the presence of RD were pT3 stage (HR 25.3; p = 0.003) and pN1 stage (HR 23.0; p = 0.022). Re-resection for iGBC is associated with improved survival but remains infrequently used and is often performed after the optimal timing interval. RD is the only significant prognostic factor for survival after re-resection and can be predicted by pT and pN stages.


β1 integrin gene excision in the adult murine cardiac myocyte causes defective mechanical and signaling responses.
How mechanical signals are transmitted in the cardiac myocyte is poorly understood. In this study, we produced a tamoxifen-inducible mouse model in which β1 integrin could be reduced specifically in the adult cardiomyocyte, so that the function of this integrin could be assessed in the postnatal and mechanically stressed heart. The expression of β1 integrin was reduced to 35% of control levels, but function remained normal at baseline. With aortic constriction, the knockout mice survived but had a blunted hypertrophic response. Integrin knockout myocytes, in contrast to controls, showed reduced integrin-linked kinase expression both at baseline and after hemodynamic stress; focal adhesion kinase expression was reduced after stress. Alterations in multiple signaling pathways were detected in the integrin knockout group after acute and chronic hemodynamic stress. Most remarkably, when we challenged the knockout mice with short-term loading, the robust responses of several kinases (extracellular signal-regulated kinase 1/2, p38, and Akt) evident in control mice were essentially abolished in the knockout mice. We also found that reduction of myocyte β1 integrin expression modified adrenergic-mediated signaling through extracellular signal-regulated kinase, p38, and Akt. Reduction of β1 integrin expression in the mature cardiac myocyte leads to a varied response compared with when this protein is reduced during either the embryonic or perinatal period. These results show that β1 integrin expression is required for proper mechanotransductive and adrenergic responses of the adult heart.


Onset and risk factors for anxiety and depression during the first 2 years after lung transplantation.
Anxiety disorders are prominent in chronic lung disease; lung transplant recipients may therefore also be at high risk for these disorders. We sought to provide the first prospective data on rates and risk factors for anxiety disorders as well as depressive disorders during the first 2 years after transplantation. A total of 178 lung recipients and a comparison group (126 heart recipients) received psychosocial and Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition assessments at 2, 7, 12, 18 and 24 months posttransplant. Survival analysis determined onset rates and risk factors. The panic disorder rate was higher (P<.05) in lung than heart recipients (18% vs. 8%). Lung and heart recipients did not differ on rates of transplant-related posttraumatic stress disorder (15% vs. 14%), generalized anxiety disorder (4% vs. 3%) or major depression (30% vs. 26%). Risk factors for disorders included pretransplant psychiatric history, female gender, longer wait for transplant, and early posttransplant health problems and psychosocial characteristics (e.g., poorer caregiver support and use of avoidant coping). Heightened vigilance for panic disorder in lung recipients and major depression in all cardiothoracic recipients is warranted. Strategies to prevent psychiatric disorder should target recipients based not only on pretransplant characteristics but on early posttransplant characteristics as well.


Effect of Active Physiotherapy With Positive Airway Pressure on Pulmonary Atelectasis After Cardiac Surgery: A Randomized Controlled Study.
The authors investigated the effect of active work with positive airway pressure (PAP) in addition to chest physiotherapy (CP) on pulmonary atelectasis (PA) in patients undergoing cardiac surgery with cardiopulmonary bypass. A randomized controlled study. At a single-center tertiary hospital. Eighty adult patients undergoing cardiac surgery (coronary artery bypass grafting, valve surgery, or both), and presenting with PA after tracheal extubation on postoperative days 1 or 2, were randomized from November 2014 to September 2016. Three days of CP, twice daily, associated with active work with PAP effect (intervention group) versus CP alone (control group). Pulmonary atelectasis was assessed by using the radiologic atelectasis score (RAS) measured from daily chest x-rays. All radiographs were reviewed blindly. Among included patients, 79 (99%) completed the trial. The primary outcome was mean RAS on day 2 after inclusion. It was significantly lower in the intervention group (mean difference and 95% CI: -1.1 [-1.6 to -0.6], p < 0.001). The secondary outcomes were the sniff nasal inspiratory pressure measured before and after CP and clinical variables. Sniff nasal inspiratory pressure was significantly higher in the intervention group on day 2 (7.7 [3.0-12.5] cmH2O, p = 0.002). The respiratory rate was lower in the intervention group (-3.2 [95% CI -4.8 to -1.6] breaths/min, p < 0.001) on day 2. No differences were found between the 2 groups for percutaneous oxygen saturation/oxygen requirement ratio, heart rate, pain, and dyspnea scores. Active work with the PAP effect, combined with CP, significantly decreased the RAS of patients undergoing cardiac surgery after 2 days of CP, with no differences observed in clinically relevant parameters.


Caterpillars Detoxify Diterpenoid from Nepeta stewartiana by the Molting Hormone Gene CYP306A1.
Herbivorous insects are well known for detoxifying a broad range of the defense compounds produced by the plants that they feed on, but knowledge of the mechanisms of detoxification is still very limited. Here, we describe a system in which two species of lepidopteran caterpillars metabolize an abietane diterpene from the plants of Nepeta stewartiana Diels to an oxygenated derivative that is less active biologically. We found that this transformation could be catalyzed by a cytochrome P450 enzyme in caterpillars, which are associated with molting. Most interestingly, abietane diterpene targets the molting-associated gene CYP306A1 to alter the content of molting hormones in the insect at specific developmental stages and competitively inhibit molting hormone metabolism. These findings identify the mechanism by which caterpillars are able to detoxify abietane diterpenoid through hydroxylation at the C-19 position, which may be opening up exciting research questions into the mechanisms of interaction between plants and insects.


PBSC mobilization, collection and positive selection in patients with chronic lymphocytic leukemia.
We report the results of PBSC mobilization and immune selection in 17 patients with advanced chronic lymphocytic leukemia (CLL) enrolled in a multicenter Italian study of autologous transplantation with peripheral CD34+ selected cells. Mobilization was achieved by cyclophosphamide (CY) 4 g/m2 + G-CSF 5 microg/kg. CD34+ cells were positively selected by means of avidin-biotin immunoaffinity columns (Ceprate SC) or immunomagnetic beads (Isolex 300i) systems. Evaluation of minimal residual disease was performed by PCR analysis of the IgH gene rearrangment on the apheresis product before and after selection. Our results showed that after CY a median of 3.6 x 10(6)/kg (0.5-12.8) CD34+ cells were collected with a median of two aphereses in 14 out of 17 patients; three failed to mobilize a number of CD34+ cells adequate for subsequent manipulation. We found that in CR patients CD34+ cell yield per apheresis was significantly higher than in PR patients (P < 0.05). Sixteen selection procedures were performed in 13 patients. CD34+ cell recovery was 33.5% (10-85) with a median final yield of 1 x 10(6)/kg CD34+. Two patients underwent marrow collection due to the low number of CD34+ cells recovered. Final purity was 59% (range 22-94) and CD5/20+ cell depletion was 2.7 log (1.6-4.4). Our data showed a statistically higher CD34+ cell recovery and purity with the Isolex device compared to Ceprate (P < 0.01 and 0.01, respectively). All the evaluable samples remained PCR positive after selection. The main issues to be addressed in the future are the identification of patients who fail mobilization and the improvement of purging methods.


Proteomics Profiling of Autologous Blood and Semen Exosomes from HIV-infected and Uninfected Individuals Reveals Compositional and Functional Variabilities.
Blood and semen are important body-fluids that carry exosomes for bioinformation transmission. Therefore, characterization of their proteomes is necessary for understanding body-fluid-specific physiologic and pathophysiologic functions. Using systematic multifactorial proteomic profiling, we characterized the proteomes of exosomes and exosome-free fractions from autologous blood and semen from three HIV-uninfected and three HIV-infected participants (total of 24 samples). We identified exosome-based protein signatures specific to blood and semen along with HIV-induced tissue-dependent proteomic perturbations. We validated our findings with samples from 16 additional donors and showed that unlike blood exosomes (BE), semen exosomes (SE) are enriched in clusterin. SE but not BE promote Protein·Nucleic acid binding and increase cell adhesion irrespective of HIV infection. This is the first comparative study of the proteome of autologous BE and SE. The proteins identified may be developed as biomarkers applicable to different fields of medicine, including reproduction and infectious diseases.


[Changes in the ventricular system of the brain in epilepsy patients (according to the results of echoventriculometry, planimetric pneumoencephalography and clinical examination)].
Examination of 120 epileptics with the use of pneumoencephalography (PEG) and echoventriculometry (EVM) demonstrated that the changes in the cerebral ventricular system could be pinpointed as early as during the first year of the disease and that later on they had a tendency for gradual progression. These changes are hardly dependent on the total duration of epilepsy but the severity of its course exerts a marked influence on them. A comparative analysis of the EVM and PEG readings as well as cerebrospinal fluid pressure values suggests that the results provided by these methods show good correlation and that in some cases it is possible to limit the work-up of patients to echoventriculometry as a sufficiently informative and safe method, without resorting to pneumoencephalography.


Neck of femur fractures in the elderly: Does every hour to surgery count?
To determine if early surgery before 12h confers a survival or length of stay benefit for patients with neck of femur (NOF) fractures. Retrospective review of prospectively collected data. District general hospital. 1913 patients aged over 60 admitted with a fractured NOF who underwent surgery between 2011 and 2015. Mean age was 83.9 years. 73.7% were female. Patients had surgery for fractured NOF with data collected on demographics, mortality and length of stay. Data collected included gender, age, ASA grade, fracture anatomy, surgery, time to surgery, days spent in acute hospital and rehabilitation settings and 30-day mortality. Statistical analysis was used to identify independent predictors of mortality and length of stay. 30-day mortality was 6.1% and the mean hospitalisation time was 13±11.3days for the acute hospital and 20.2±17.2days for the trust. Operations were performed at a mean of 23.8±14.8h after presentation. Age, gender, ASA grade and type of fracture were independent predictors of either mortality or length of stay. Timing of surgery had an association with mortality but this only reached statistical significance at 24h. In line with previous studies we analysed time to surgery in 12h blocks. We also used logistic regression, recognizing time as a continuous variable, which revealed that every hour of delay to surgery increased the mortality risk by 1.8%. While every hour of delay increased mortality risk, the association with mortality only became statistically significant when delaying over 24h. This supports a pragmatic approach, with surgery as soon as medically possible without a race to theatre. Level III retrospective cohort study.


Plasmid CpG depletion improves degree and duration of tumor gene expression after intravenous administration of polyplexes.
Tumor gene expression after the intravenous (i.v.) administration of current polymer-based gene delivery systems is generally low and short-lived. Immune stimulatory CpG dinucleotides, present within the plasmid DNA of the polyplexes are likely to contribute to this. The effect of CpG replacement on the levels of transgene expression was studied, after the i.v. administration of polyethylenimine (PEI) polyplexes. Tumor transfection and immune stimulation of PEI polyplexes containing plasmid DNA encoding for luciferase and rich in CpG motifs was monitored and compared to polyplexes containing the same gene but devoid of CpG motifs. Lipoplexes based on 1,2-dioleyl-3-trimethylammonium-propane/dioleoylphosphatidylethanolamine liposomes were included as a control. The replacement of CpGrich DNA by CpGfree DNA did neither affect the physical properties of the DNA complexes nor did it affect their in vitro transfection activity or cytotoxicity. The immune stimulation (interleukin-12) after i.v. administration of the PEI DNA complexes was low and unaffected by the presence of CpG motifs. The absence of CpG motifs within the different DNA complexes improved the degree and the duration of organ and tumor gene expression. The depletion of CpG dinucleotides within the plasmid DNA of polyplexes enhances the degree and duration of in vivo transgene expression.


Putaminal lesion in multiple system atrophy: postmortem MR-pathological correlations.
Posterior putaminal atrophy, putaminal T2-hyper and/or hyposignal changes have been observed in patients with multiple system atrophy (MSA) with parkinsonism. Postmortem T2-weighted images were compared with histological findings in seven autopsy-proven cases of putaminal lesions of MSA. All cases were evaluated on 1.5T magnetic resonance imaging (MRI) scanners and three cases were evaluated on 3T scanners. There were three types of putaminal changes: Type 1, mild putaminal atrophy and isointensity; Type 2, putaminal atrophy and diffuse hyperintensity with a hyperintense putaminal rim (HPR); Type 3, putaminal atrophy and iso-or-hypointensity with HPR. The signal intensities of the putamen in Types 1 and 3 were more hypointense on 3T images than on 1.5T images. In Type 1, mild putaminal atrophy showed mild neuronal loss and gliosis and diffuse ferritin deposition. In Types 2 and 3, the areas of putaminal atrophy, severe in the posterior region, showed severe neuronal loss and gliosis, many pigments that were positive for ferritin and Fe (3+) and diffuse ferritin deposition. Although, tissue rarefaction was more severe in Type 2 than in Type 3, pigment deposition was more severe in Type 3. The HPR showed a severe loss of myelin and axons with tissue rarefaction of the external capsule or putaminal rim in Types 2 and 3. Posterior putaminal atrophy reflects neuronal loss and gliosis. While putaminal iso-or -hypointensity reflects diffuse ferritin and Fe(3+) deposition, hyperintensity reflects tissue rarefaction. The HPR reflects degeneration of the putaminal lateral margin and/or external capsule. These findings reflect characteristic histological findings of MSA with parkinsonism.


Inhibition of dopamine biosynthesis by tetrahydropapaveroline.
Tetrahydropapaveroline (THP) at 5-15 microM has been found to induce L-DOPA-induced oxidative apoptosis in PC12 cells. In this study, the inhibitory effects of THP on dopamine biosynthesis in PC12 cells and tyrosine hydroxylase (TH) activity in bovine adrenal were investigated. Treatment of PC12 cells with THP at 2.5-10 microM significantly decreased the intracellular dopamine content in a concentration-dependent manner (21.3% inhibition at THP 10 microM). The activity of TH was also inhibited by the treatment with THP at 2.5-10 microM (23.4% inhibition at 10 microM). In addition, THP had an inhibitory effect on bovine adrenal TH (IC50 value, 153.9 microM). THP exhibited uncompetitive inhibition on bovine adrenal TH with a substrate l-tyrosine with the Ki value with L-tyrosine of 0.30 mM. Treatment with L-DOPA at 20-50 microM increased the intracellular dopamine content in PC12 cells and the increase in dopamine content by L-DOPA was in part inhibited when L-DOPA (20 and 50 microM) was associated with THP at non-cytotoxic (5-10 microM) or cytotoxic (15 microM) concentration ranges. However, the reduction of dopamine content by THP (15 microM) or THP (15 microM) associated with L-DOPA (20 and 50 microM) in PC12 cells was inversed by the antioxidant N-acetyl-cysteine (0.1mM). These results indicate that THP at 5-10 microM decreases the basal dopamine content and reduces the increased dopamine content induced by L-DOPA in part by the inhibition of TH activity, and that THP at 15 microM does by oxidative stress in PC12 cells.


A risk-benefit analysis of alternating low-pressure CO2 insufflation and fluid medium in arthroscopic knee ACL reconstruction.
The purpose of this study was to test the hypothesis that the surgical technique using alternating fluid irrigation and carbon dioxide (CO2) gas medium as a means of knee joint distension during arthroscopy is a safe and effective method, compared to traditional fluid arthroscopy. This prospective randomized comparative study involved 94 patients undergoing the same arthroscopic ACL reconstruction surgical procedure except for the medium used to distend the joint: In a first group of 48 patients ("ACL gas" group), CO2 insufflation was mainly used, at a low pressure of 40-50 mmHg, alternating with a fluid medium for knee joint washout only. In the second group of 46 patients, classical arthroscopic joint distension by fluid was used, with a pump pressure of 50-70 mmHg. Early pre- and post-operative complications, duration of surgery, intraoperative monitoring data and particularly the end-tidal carbon dioxide (EtCO2) as a marker of CO2 blood diffusion were prospectively collected. EtCO2 and other monitoring data changes before and after tourniquet release were not different between the two groups. Tourniquet time was significantly longer when using fluid rather than gas. We observed 3 cases of small and localized subcutaneous emphysema, resolving completely within hours. Hematoma and reflex sympathetic dystrophy occurred more often in the "ACL fluid" group, with no statistical significance. Low-pressure CO2 knee joint insufflation proved to be a safe technique capable of improving surgical comfort compared with the use of fluid alone. The CO2 blood diffusion measured by end-tidal carbon dioxide monitoring during ACL arthroscopic reconstruction was similar with or without gas insufflation.


[Dynamic range of acoustic reflex and its importance for hearing aid evaluation (author's transl)].
It is reported on the dynamic range of acoustic reflex in the case of normal hearing. Stimulation is carried out with speech noise under free field conditions. The sensitivity of impedance measurement is increased by using an averager, which enables acoustic reflex measurements at sound pressure levels of about 70 dB. Further an exact evaluation of input-output-characteristics becomes possible by this procedure. Basing on this consideration the possibility of objective hearing aid evaluation is discussed. The fundamental point of this technique should be the compensation of pathological input-output-characteristics by suitable hearing aids.


The landscape complexity relevance to farming effect assessment on small mammal occupancy in Argentinian farmlands.
The responses of organisms to organic farming depend on the taxonomic group and landscape complexity. Following the intermediate landscape complexity hypothesis, organic farming can compensate for the lack of complexity in simple landscapes. Argentinian farmlands are simple with large fields and scarce linear habitat array, and conventional agriculture is almost the only agriculture practice. We hypothesize that there is an interaction effect of landscape complexity and farming practices on occupancy and species richness of small mammals in farmland of central Argentina. We selected circular landscapes under organic farming and low- and high-intensity conventional farming and quantified heterogeneity in each landscape considering different cover types (crops, resting plots, fallow land, border habitats, grasslands and man-made structures). We used multi-species occupancy models accounting for multiple seasons with a Bayesian approach to make the estimates. Landscapes under organic farms had the highest level of landscape heterogeneity. In simple Argentinian farmlands, organic farming benefited species richness and occupancy of all small mammal species. Some management strategies used in organic farming (wide and vegetated border habitats, diversity in types of production, winter cover crops, natural or semi-natural patches) should be taken into account to increase landscape complexity in conventional farming.


Nuclear matrix bound terminal deoxynucleotidyl transferase in rat thymus nuclei. II. Effect of ATP on free and matrix bound TdT.
Endogenous nuclease digestion of thymus nuclei from 3-4 week old rats followed by a step wise extraction with low salt, 0.5 M salt and 1 M salt removed approximately 70-85% of total nuclear terminal deoxynucleotidyl transferase (TdT) whereas approximately 15-30% of the enzyme remained tightly bound to the residual nuclear matrix. The cytoplasmic TdT as well as the bulk of nuclear TdT extracted in low salt and 0.5 M salt was found to be strongly inhibited at low concentration of ATP whereas matrix bound TdT and a significant portion of the enzyme in 1 M salt extract was completely insensitive to this nucleotide. The ATP resistant enzyme in the 1 M salt extract was unstable and slowly converted to ATP sensitive form upon prolonged preincubation on ice whereas under similar conditions it remained unaffected in the matrix bound form. These observations lead us to suggest that ATP resistant matrix bound TdT being capable of discriminating unnatural rNTPs against the natural dNTP substrates, may be the functionally organized form of the enzyme and that free TdT having lost the capability to distinguish between dNTP and rNTP may be the nonfunctional form of the enzyme in the thymus gland.


Hippo/MST blocks breast cancer by downregulating WBP2 oncogene expression via miRNA processor Dicer.
WBP2 transcription coactivator is an emerging oncoprotein and a key node of convergence between EGF and Wnt signaling pathways. Understanding how WBP2 is regulated has important implications for cancer therapy. WBP2 is tightly controlled by post-translational modifications, including phosphorylation and ubiquitination, leading to changes in subcellular localization, protein-protein interactions, and protein turnover. As the function of WBP2 is intricately linked to YAP and TAZ, we hypothesize that WBP2 is negatively regulated by the Hippo tumor suppressor pathway. Indeed, MST is demonstrated to negatively regulate WBP2 expression in a kinase-dependent but LATS-independent manner. This was observed in the majority of the breast cancer cell lines tested. The effect of MST was enhanced by SAV and concomitant with the inhibition of the transcription co-activation, in vitro and in vivo tumorigenesis activities of WBP2, resulting in good prognosis in xenografts. Downregulation of WBP2 by MST involved miRNA but not proteasomal or lysosomal degradation. Our data support the existence of a novel MST-Dicer signaling axis, which in turn regulates both WBP2 CDS- and UTR-targeting miRNAs expression, including miR-23a. MiR-23a targets the 3'UTR of WBP2 mRNA directly. Significant inverse relationships between WBP2 and MST or miR23a expression levels in clinical specimens were observed. In conclusion, WBP2 is a target of the Hippo/MST kinase; MST is identified as yet another rheostat in the regulation of WBP2 and its oncogenic function. The findings have implications in targeted therapeutics and precision medicine for breast cancer.


Virus infection in demyelinating diseases.
Several animal and human demyelinating diseases of the central nervous system (CNS) are associated with RNA or DNA viruses. These viruses infect CNS cells lytically or persistently. They mainly belong to the group of envelope viruses which derive their envelope partly from the host cell membrane. The process of virus release may result in the appearance of new antigens of virus-infected cells or the incorporation of cell membrane material into the viral envelope. These changes may lead to an immune response which selectively injures the CNS. These alterations of host cell membranes and host cell functions, together with the immune mechanism, are central to many of the hypotheses regarding virus-induced demyelination. The role of virus infection in progressive multifocal leukoencephalopathy, subacute sclerosing panencephalitis, visna and mouse hepatitis virus infections, is discussed in relation to the demyelinating process of these diseases.


Acute sinusitis in children: diagnosis and management.
Acute sinusitis is a common problem in children that is often overlooked. The pathophysiology is related to obstruction of the sinus ostia and mucociliary dysfunction. The predominant pathogens include Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. The diagnosis of acute sinusitis is based on persistent or severe upper respiratory tract symptoms. The routine use of roentgenograms to confirm the diagnosis of uncomplicated sinusitis is not recommended for children 6 years or younger but may be considered for children older than 6 years. Antimicrobial therapy is the cornerstone of management and amoxicillin is the drug of choice for most cases of uncomplicated sinusitis.


Growth, biomass distribution and CO2 exchange of northern hardwood seedlings in high and low light: relationships with successional status and shade tolerance.
The physiology, morphology and growth of first-year Betula papyrifera Marsh., Betula alleghaniensis Britton, Ostrya virginiana (Mill.) K. Koch, Acer saccharum Marsh., and Quercus rubra L. seedlings, which differ widely in reported successional affinity and shade tolerance, were compared in a controlled high-resource environment. Relative to late-successional, shade-tolerant Acer and Ostrya species, early-successional, shade-intolerant Betula species had high relative growth rates (RGR) and high rates of photosynthesis, nitrogen uptake and respiration when grown in high light. Fire-adapted Quercus rubra had intermediate photosynthetic rates, but had the lowest RGR and leaf area ratio and the highest root weight ratio of any species. Interspecific variation in RGR in high light was positively correlated with allocation to leaves and rates of photosynthesis and respiration, and negatively related to seed mass and leaf mass per unit area. Despite higher respiration rates, early-successional Betula papyrifera lost a lower percentage of daily photosynthetic CO2 gain to respiration than other species in high light. A subset comprised of the three Betulaceae family members was also grown in low light. As in high light, low-light grown Betula species had higher growth rates than tolerant Ostrya virainiana. The rapid growth habit of sarly-successional species in low light was associated with a higher proportion of biomass distributed to leaves, lower leaf mass per unit area, a lower proportion of biomass in roots, and a greater height per unit stem mass. Variation in these traits is discussed in terms of reported species ecologies in a resource availability context.


Microtiter micromass cultures of limb-bud mesenchymal cells.
A method is described for growing high-density micromass cultures of chick and mouse limb mesenchyme cells in 96-well microtiter plates (microT microM cultures). Rapid quantitative estimates of chondrogenic expression were obtained by automated spectrophotometric analysis of Alcian-blue-stained cartilage matrix extracts performed in the wells in which the cells had been grown. Quantitative estimates of myogenic expression were obtained similarly using anti-sarcomere myosin monoclonal antibody and modified ELISA techniques. This microT microM-ELISA method may be adapted for use with other antigens for which specific antibodies are available. These methods were used to compare cartilage and muscle differentiation in 1 to 4 d microT microM cultures grown in serum-containing (SCM) and defined (DM) media. The DM contains minimal additives (insulin, hydrocortisone, and in some cases, ascorbate or transferrin) and supports both chondrogenesis and myogenesis. The colorimetric analyses agree well with the morphologic appraisal of chondrogenesis and myogenesis. Similar numbers of cartilage nodules formed in all cultures, but in DM the nodules failed to enlarge; explaining the reduced matrix synthesis in DM as compared with SCM, and suggesting that nodule enlargement is a discrete, serum-dependent step. Studies of selected additives to DM show that transferrin enhances myogenesis, ascorbic acid enhances chondrogenesis, and retinoic acid inhibits chondrogenesis. Together, the microT microM system, in situ colorimetric assays of chondrogenesis and myogenesis, and DM will allow rapid prescreening of teratogens and screening of various bioactive compounds (e.g., hormones, growth factors, vitamins, adhesion factors) for effects on limb mesenchymal cell differentiation.


The First Bacterial Endocarditis Due to Achromobacter xylosoxidans in a Dog.
Infectious endocarditis (IE) in dogs is often associated with a high mortality rate as diagnostic work-up as well as antibiotic treatment might be challenging. The present case describes bacteremia in a dog caused by Achromobacter xylosoxidans, leading to an infectious endocarditis. Achromobacter xylosoxidans (A. xylosoxidans) is an aerobic Gram-negative rod-shaped bacterium, which has been associated with multiple nosocomial opportunistic diseases in human medicine. One such manifestation of A. xylosoxidans infection is endocarditis. A. xylosoxidans infections are challenging to treat due to the reduced effectiveness of a wide range of antimicrobial agents. To date, only a few case reports of infections with A. xylosoxidans in animals have been described. This is the first case report of A. xylosoxidans endocarditis in a dog. Whole-genome sequencing was performed to determine the sequencing type and to gain more information about this bacterium regarding its intrinsic resistance genes. With this case report, we seek to increase awareness of A. xylosoxidans as an opportunistic nosocomial pathogen in dogs and to provide a short summary regarding the current state of general knowledge and known resistance patterns.


Thoracotomy as a staging procedure after chemotherapy in the treatment of Stage III nonseminomatous carcinoma of the testis.
Of 108 patients with a nonseminomatous testicular carcinoma, 28 with lung metastases were studied. After combination chemotherapy with cisplatin, vinblastine, and bleomycin (PVB), 11 patients underwent exploratory thoracotomy. Viable carcinomatous tissue, along with fibrosis, necrosis, and mature teratoma, was found in 4 patients. Three of these patients were successfully retreated with VP 16-213, cisplatin, and actinomycin D. In patients with residual pulmonary or mediastinal masses after chemotherapy, resection of the lesions is mandatory to demonstrate viable carcinoma so that treatment can be readministered. Thus, in our view, thoracotomy is a diagnostic procedure.


Effects of purified myosin light chain kinase on myosin light chain phosphorylation and catecholamine secretion in digitonin-permeabilized chromaffin cells.
Many non-muscle cells including chromaffin cells contain actin and myosin. The 20,000 dalton light chain subunits of myosin can be phosphorylated by a Ca2+/calmodulin-dependent enzyme, myosin light chain kinase. In tissues other than striated muscle, light chain phosphorylation is required for actin-induced myosin ATPase activity. The possibility that actin and myosin are involved in catecholamine secretion was investigated by determining whether increased phosphorylation in the presence of [gamma-32P]ATP of myosin light chain by myosin light chain kinase enhances secretion from digitonin-treated chromaffin cells. In the absence of exogenous myosin light chain kinase, 1 microM Ca2+ caused a 30-40% enhancement of the phosphorylation of a 20 kDa protein. This protein was identified on 2-dimensional gels as myosin light chain by its comigration with purified myosin light chain. Purified myosin light chain kinase (400 micrograms/ml) in the presence of calmodulin (10 microM) caused little or no enhancement of myosin light chain phosphorylation in the absence of Ca2+ in digitonin-treated cells. In the presence of 1 microM Ca2+, myosin light chain kinase (400 micrograms/ml) caused an approximately two-fold increase in myosin light chain phosphorylation in digitonin-treated cells in 5 min. The phosphorylation required permeabilization of the cells by digitonin and occurred within the cells rather than in the medium. Myosin light chain kinase-induced phosphorylation of myosin light chain was maximal at 1 microM Ca2+. Under identical conditions to those of the phosphorylation experiments, secretion was unaltered by myosin light chain kinase. The experiments indicate that the phosphorylation of myosin light chain by myosin light chain kinase is not a limiting factor in secretion in digitonin-treated chromaffin cells and suggest that the activation of myosin is not directly involved in secretion from the cells. The experiments also demonstrate the feasibility of investigation of effects of exogenously added proteins on secretion in digitonin-treated cells.


Downregulation of miR-223 promotes HMGB2 expression and induces oxidative stress to activate JNK and promote autophagy in an in vitro model of acute lung injury.
Excessive autophagic activity in alveolar epithelial cells is one of the main causes of acute lung injury (ALI), but the underlying molecular mechanism has not been fully elucidated. Previous studies have shown that microRNAs (miRs) are involved in regulating autophagy in several diseases. This study aimed to determine the role of miR-223 in excessive autophagic activity in alveolar epithelial cells and the underlying mechanism to identify a novel therapeutic targets for the development of new drugs to treat acute respiratory distress syndrome (ARDS). A549 cells were treated with lipopolysaccharide (LPS) to establish an ALI in vitro model. The expression of miR-223 and its role of miR-223 in regulating oxidative stress and autophagy in the LPS-treated A549 cells, were examined using RT-PCR, flow cytometry and ELISA. A luciferase reporter assay was performed to verify the interaction between miR-223 and the high-mobility group box 2 (HMGB2) protein. The results showed that the LPS treatment downregulated miR-223 expression in alveolar epithelial cells. We further proved that miR-223 directly targeted the 3-untranslated region of the HMGB2 gene and the downregulation of miR-223 increased HMGB2 protein level, which activated the JNK signalling pathway and thus induced oxidative stress and autophagy in LPS-treated alveolar epithelial cells. Knockdown of HMGB2 protein deactivated the JNK signalling pathway and inhibited autophagy and oxidative stress in alveolar epithelial cells. The results of this study suggest that miR-223 regulates oxidative stress and autophagy in alveolar epithelial cells by targeting HMGB2 via the JNK signalling pathway.


Lagging strand DNA synthesis at the eukaryotic replication fork involves binding and stimulation of FEN-1 by proliferating cell nuclear antigen.
The 5'-->3'-exonuclease domain of Escherichia coli DNA polymerase I is required for the completion of lagging strand DNA synthesis, and yet this domain is not present in any of the eukaryotic DNA polymerases. Recently, the gene encoding the functional and evolutionary equivalent of this 5'-->3'-exonuclease domain has been identified. It is called FEN-1 in mouse and human cells and RTH1 in Saccharomyces cerevisiae. This 42-kDa enzyme is required for Okazaki fragment processing. Here we report that FEN-1 physically interacts with proliferating cell nuclear antigen (PCNA), the processivity factor for DNA polymerases delta and epsilon. Through protein-protein interactions, PCNA focuses FEN-1 on branched DNA substrates (flap structures) and on nicked DNA substrates, thereby stimulating its activity 10-50-fold but only if PCNA can functionally assemble as a toroidal trimer around the DNA. This interaction is important in the physical orchestration of lagging strand synthesis and may have implications for how PCNA stimulates other members of the FEN-1 nuclease family in a broad range of DNA metabolic transactions.


[Benign and malignant tumors of the thoracic skeleton after percutaneous radiotherapy of Hodgkin's and non-Hodgkin's lymphomas].
Disorders of the skeleton in the thoracic area after percutaneous irradiation of malignant lymphomas are relatively rare. The most common site for pathologic changes is the clavicula. Local overdosage and, in case of malignant alterations, an additional chemotherapy might be the reasons. Among our patients seven lesions occurred, three of them were malignant: two osteogenic sarcomas and one chondrosarcoma.


Cellular and molecular characteristics of pollen abortion in chrysanthemum cv. Kingfisher.
Microspore degeneration at the tetrad stage is associated with tapetum degeneration retardation. Some genes and proteins related to cell senescence and death are the key factors for pollen abortion. Chrysanthemum (Chrysanthemum morifolium) is a major floriculture crop in the world, but pollen contamination is an urgent problem to be solved in chrysanthemum production. C. morifolium 'Kingfisher' is a chrysanthemum cultivar that does not contain any pollen in mature anthers, thus it is a very important material for developing chrysanthemum without pollen contamination. However, the mechanism of its pollen abortion remains unclear. In this study, the cellular and molecular mechanisms of 'Kingfisher' pollen abortion were investigated using transmission electron microscopy, RNA sequencing, isobaric tags for relative and absolute quantitation, and bioinformatics. It was found that the meiosis of microspore mother cells was normal before the tetrad stage, the microspores began to degenerate at the tetrad stage, and no microspores were observed in the anthers after the tetrad stage. In addition, transcriptomic and proteomic analyses showed that some genes and proteins related to cell senescence and death were identified to be implicated in chrysanthemum pollen abortion. These results indicated that the tetrad stage was the main period of pollen abortion, and the genes and proteins related to cell senescence and death contributed to pollen abortion. These add to our understanding of chrysanthemum pollen abortion and will be helpful for development of flowers without pollen contamination in the future.


Optimization of alkaline protease production by Aspergillus clavatus ES1 in Mirabilis jalapa tuber powder using statistical experimental design.
Medium composition and culture conditions for the bleaching stable alkaline protease production by Aspergillus clavatus ES1 were optimized. Two statistical methods were used. Plackett-Burman design was applied to find the key ingredients and conditions for the best yield. Response surface methodology (RSM) including full factorial design was used to determine the optimal concentrations and conditions. Results indicated that Mirabilis jalapa tubers powder (MJTP), culture temperature, and initial medium pH had significant effects on the production. Under the proposed optimized conditions, the protease experimental yield (770.66 U/ml) closely matched the yield predicted by the statistical model (749.94 U/ml) with R (2)=0.98. The optimum operating conditions obtained from the RSM were MJTP concentration of 10 g/l, pH 8.0, and temperature of 30 degrees C, Sardinella heads and viscera flour (SHVF) and other salts were used at low level. The medium optimization contributed an about 14.0-fold higher yield than that of the unoptimized medium (starch 5 g/l, yeast extract 2 g/l, temperature 30 degrees C, and pH 6.0; 56 U/ml). More interestingly, the optimization was carried out with the by-product sources, which may result in cost-effective production of alkaline protease by the strain.


Photocatalytic degradation of p-nitrophenol on nanometer size titanium dioxide surface modified with 5-sulfosalicylic acid.
The surface of nanometer size TiO(2) was simply and fast modified by chemical adsorption in saturated solution of 5-sulfosalicylic acid. After surface modification, a stable, yellow surface complex was formed quickly, the wavelength response range of TiO(2) was expanded, it has obvious absorption in the region from 320 to 450 nm; the adsorption efficiency of p-nitrophenol (PNP) by TiO(2) was enhanced from 42% to 84%. The photocatalytic activity was tested on the degradation of PNP. The influences of catalyst and its dosage, pH value, and PNP concentration on the degradation were investigated. On optimal photodegradation conditions, including initial pH 4.0, PNP 5 mg l(-1), catalyst 100 mg, irradiation time 120 min with 160 W high-pressure mercury lamp, the degradation efficiency of PNP was increased from 40% to 88% after surface modification. Surface modification led not only to an increase in the light utilization, but also improved the surface coverage of PNP in comparison with the pure TiO(2). Both of these factors are crucial for the photocatalytic activity of heterogeneous photocatalysis, especially for photodegradation of benzenoid pollutants.


Using Andersen's behavioral model of health care use for intermittent preventive treatment of malaria in pregnancy in Nigeria.
Studies in Nigeria and elsewhere in sub-Saharan Africa (sSA) have explored factors influencing usage of intermittent preventive treatment of malaria in pregnancy (IPTp). Most studies, however, are not model or theory-based, which provides less satisfactory guidance to malaria control programming. This study fills the knowledge gap by adapting Andersen's behavioral model of health care use to IPTp usage in Nigeria. This study adopted a cross-sectional design that utilized secondary data extracted from the 2018 Nigeria Demographic and Health Survey (NDHS). A weighted sample of 4,772 women who had given birth in the past year preceding the survey, was analyzed. Outcome variable was usage of IPTp, dichotomized into optimal or otherwise. Explanatory variables cut across individual and community levels and were divided into predisposing, enabling and need factors in line with the theoretical constructs of the Andersen model. Two multilevel mixed-effects logistic regression models were fitted to identify factors which influenced optimal usage of IPTp. Analyses were performed using STATA 14. Statistical significance was set at 5%. Realised level of optimal IPTp usage was 21.8%. Factors that either predispose or enable pregnant women to take optimal doses of IPTp were maternal education, being employed, being autonomous in their own healthcare, health insurance enrolment, partner education, receiving antenatal care in public health facilities, rural residence, being resident in northern geo-political zones, community literacy level and community perception of the consequences of malaria. Two significant need factors affecting optimal usage of IPTp were timing of the first antenatal care visit and sleeping under mosquito bed nets. Optimal usage of IPTp is low among pregnant women in Nigeria. There is a need to devise additional public health educational programs promoting IPTp usage through the formation of Advocacy, Communication and Social Mobilisation (ACSM) in every ward in all local government areas, particularly in the rural and northern parts of the country. In addition, health planners should adopt the Andersen model for assessing key determinants of IPTp usage among childbearing women in Nigeria.


How heavy metal stress affects the growth and development of pulse crops: insights into germination and physiological processes.
The current work is an extensive review addressing the effects of heavy metals in major pulse crops such as Chickpea (Cicer arietinum L.), Pea (Pisum sativum L.), Pigeonpea (Cajanus cajan L.), Mung bean (Vigna radiata L.), Black gram (Vigna mungo L.) and Lentil (Lens culinaris Medik.). Pulses are important contributors to the global food supply in the world, due to their vast beneficial properties in providing protein, nutritional value and health benefits to the human population. Several studies have reported that heavy metals are injurious to plants causing inhibition in plant germination, a decrease in the root and shoot length, reduction in respiration rate and photosynthesis. Properly disposing of heavy metal wastes has become an increasingly difficult task to solve in developed countries. Heavy metals pose one of the substantial constraints to pulse crops growth and productivity even at low concentrations. This article attempts to present the morphological, biochemical and various physiological changes induced on the pulse crops grown under various heavy metal stress such as As, Cd, Cr, Cu, Pb, and Ni.


TRAF5-mediated Lys-63-linked Polyubiquitination Plays an Essential Role in Positive Regulation of RORγt in Promoting IL-17A Expression.
Retinoid-related orphan nuclear receptor γt (RORγt) is a key transcription factor for the development and function of Th17 cells. In this study, we show that tumor necrosis factor receptor-associated factor 5 (TRAF5), known as an E3 ubiquitin protein ligase and signal transducer, interacts with and ubiquitinates RORγt via Lys-63-linked polyubiquitination. TRAF5 stabilizes the RORγt protein level depending on its RING finger domain. Depletion of TRAF5 in Th17 cells destabilizes RORγt protein and down-regulates Th17-related genes, including IL-17A, an inflammatory cytokine involved in pathogenic mechanisms of several autoimmune diseases such as systemic lupus erythematosus. Moreover, up-regulation of the TRAF5 mRNA level was found in systemic lupus erythematosus patient CD4(+) T cells. Our findings reveal a direct link between TRAF5-mediated ubiquitination and RORγt protein regulation, which may aggravate inflammatory progress and provide new therapeutic drug targets for autoimmune diseases.


Haemangiomas around the knee mimicking medial meniscal tears. Report of two cases and review of the literature.
There are few reports in the English literature of extra-articular lesions simulating intra-articular pathology of the knee. Two cases of histologically confirmed haemangiomas related to the distal femur, presenting with knee pain suggestive of medial meniscal damage, are reported. A 27-year-old woman presented with persistent anteromedial right knee pain despite having undergone two arthroscopies for medial meniscal damage. An MRI showed a soft tissue mass on the medial side of the distal femoral metaphysis. The symptoms resolved only after open resection of the lesion. Histology showed a periosteal haemangioma. The second patient, a 24-year-old woman, complained of posteromedial left knee pain for 3 months. Although a medial meniscal tear was suspected, an MRI showed a soft tissue mass close to the bone of the distal femoral diaphysis. The symptoms resolved after open resection of the lesion. Histology showed a soft tissue haemangioma. Both patients were asymptomatic with normal MRI scans 6 to 12 months postoperatively. Although meniscal tears can present in young patients without a history of trauma, an MRI is extremely useful in diagnosing other lesions causing similar symptoms. Haemangiomas around the knee are rare, in particular periosteal haemangiomas of the distal femur as no report has been found in the English literature.


[Everyday psychiatry--a contribution to the hermeneutics of diagnostic and therapeutic clinical practice].
The relations between diagnostic and therapeutic practice and the events of everyday life are investigated in a two-fold regard. The first view is directed towards the signification of "psychiatry" and of the psychiatric view-points in the everyday life of society; the second view is the experience of everyday life inside psychiatric institutions. Under both aspects an interest in the development and the both aspects an interest in the development and the process of mental illness is pursued, which is also an interest in correct diagnostic insight and in promoting therapeutic consequence that positively influences the process.


Acupoint Injection Decreases Anesthetic Cosumption during Combined Spinal-Epidural and Patient-Controlled Epidural Labor Analgesia.
To explore if acupoint injection can improve analgesic effects or delivery outcomes in parturients who received combined spinal-epidural analgesia (CSEA) and patient-controlled epidural analgesia (PCEA) for labor analgesia. A total of 307 participants were prospectively collected from July 2017 to December 2019. The participants were randomized into the combined acupoint injection with CSEA plus PCEA group (AICP group, n=168) and CSEA plus PCEA group (CP group, n=139) for labor analgesia using a random number table. Both groups received CSEA plus PCEA at cervical dilation 3 cm during labor process, and parturients of the AICP group were implemented acupoint injection for which bilateral acupoint of Zusanli (ST 36) and Sanyinjiao (SP 6) were selected in addition. The primary outcome was Visual Analogue Scale (VAS) score, and the secondary outcomes were obstetric outcomes and requirement of anesthetics doses. Safety evaluations were performed after intervention. The VAS scores were significantly lower in the AICP group than in the CP group at 10, 30, 60, and 120 min after labor analgesia (all P<0.05). The latent phase of the AICP group was shorter than that of the CP group (P<0.05). There were less additional anesthetics consumption, lower incidences of uterine atony, fever, pruritus and urinary retention in the AICP group than those in the CP group (all P<0.05). Acupoint injection combined CSEA plus PCEA for labor analgesia can decrease the anesthetic consumption, improve analgesic quality, and reduce adverse reactions in the parturients. (Registration No. ChiMCTR-2000003120).


Dibasic benzo[b]thiophene derivatives as a novel class of active site directed thrombin inhibitors. 2. Exploring interactions at the proximal (S2) binding site.
In an effort to increase the thrombin inhibitory activity of a novel series of inhibitors (i.e., 1a), substituents were incorporated at the C-3" position of the C-3 aryl ring (2). Consistent with the X-ray crystallography studies, small hydrophobic groups at the C-3" site (Br and Me) enhanced thrombin inhibitory activity by 8-fold. However, a few more hydrophilic substituents (NO2 and OMe) also enhanced the potency of the series. The biological results are discussed in terms of molecular modeling studies.