Hemoglobin Kinetics of the Galapagos Rift Vent Tube Worm Riftia pachyptila Jones (Pogonophora; Vestimentifera).
Kinetics of the reactions of Riftia pachyptila hemoglobin with oxygen were followed spectrophotometrically by stopped-flow and laser flash photolysis techniques. The rate of oxygen dissociation increases eightfold over the range of 5 degrees to 20 degrees C (k = 2.2 sec(-1)at 10 degrees C). Oxygen recombination after flash photolysis was biphasic. The rates of both slow and fast phases of the reaction were independent of temperature from 0 degrees to 20 degrees C(k'fast = 7 x 10(6); k'slow = 1 x 16(6) liter mole (-1) sec(-1)). As the oxygen affinity is relatively temperature independent, analysis in terms of the two-state model of cooperativity requires that the conformational equilibrium constant L decrease by about 50-fold between 3 degrees and 15 degrees C.


Covid-19 and medical liability: A delicate balance.
During the Covid-19 pandemic, many countries around the world are considering whether and how to provide liability protection to front-line healthcare staff. The guiding principle of liability protection for physicians and others is to ensure that, in a serious emergency situation, health professionals can devote themselves exclusively to their work and to patient care, without the fear of future claims for unforeseeable, but above all unavoidable, injury, loss and damage caused by their conduct. Great care is needed to balance the interests and rights of all those involved. Liability protection could have risky consequences with the final result that doctors will not be protected, but institutions such as health facilities will be even if they were in fact responsible for foreseeable and avoidable damage.


Caregiver stress in stroke survivor: data from a tertiary care hospital -a cross sectional survey.
A principal caregiver (CG) is directly affected by patient's health problems that lead to CG strain. Pakistan has an estimated 4.8% of the population suffering from strokes. The study objective was to evaluate the caregiver level of stress and the factors which make CGs more prone to stress and also to identify the predictive role of factors such as age, sex, educational, marital status on their burden. This was a cross-sectional survey. 112 Participants were chosen on the basis of being directly involved in the care of patient and able to give consent for the study. Stroke patients had to have a more than 1 month history of stroke and treated in a tertiary care hospital. The severity of stress was rated using the Modified Caregiver Strain Index (MCSI). Out of a total of 112 stroke patients and their caregivers, 12 were exempted. Most of the CGs were between the ages 30-39 (48%) and male (70%). Out of the males, most were sons (89%). None of the female CGs was employed. The mean MCSI score was 13.8. Gender, age, marital status, and duration of care all did not have a significant effect on the total (P = 0.640, 0.848, 0.839, 0.110 respectively). Female gender (P = 0.0075) was a factor leading to increased emotional adjustments. Single CGs had increased changes in personal plans (P = 0.014), and married CGs found the behaviour of the patients less upsetting (P = 0.0425). There was no significant difference between the total (P = 0.906) or individual components between daughters and daughter-in-laws. Increased duration of care was significantly associated with decrease level of sleep disturbance (P = 0.026), physical strain (P = 0.050) and other demands on time (P = 0.044). Increase age of CG was associated with an increase feeling of being overwhelmed (P = 0.027). There is a need to identify the factors responsible for major CG stress by conducting similar studies and to define structured intervention for evaluating and preventing problems of caregivers.


A model-based reconstruction technique for quantitative myocardial perfusion imaging.
To reduce saturation effects in the arterial input function (AIF) estimation of quantitative myocardial first-pass saturation recovery perfusion imaging by employing a model-based reconstruction. Imaging was performed with a saturation recovery prepared radial FLASH sequence. A model-based reconstruction was applied for reconstruction. By exploiting prior knowledge about the relaxation process, an image series with different saturation recovery times was reconstructed. By evaluating images with an effective saturation time of approximately 3 ms, saturation effects in the AIF determination were reduced. In a volunteer study, this approach was compared with a standard prebolus technique. In comparison to the low-dose injection of a prebolus acquisition, saturation effects were further reduced in the AIFs determined using the model-based approach. These effects, which were clearly visible for all six volunteers, were reflected in a statistically significant difference of up to 20% in the absolute perfusion values. The application of model-based reconstruction algorithms in quantitative myocardial perfusion imaging promises a significant improvement of the AIF determination. In addition to greatly reducing saturation effects that occur even for the prebolus methods, only a single bolus has to be applied. Magn Reson Med 76:880-887, 2016. © 2015 Wiley Periodicals, Inc.


Multicenter fresh frozen tissue sampling in colorectal cancer: does the quality meet the standards for state of the art biomarker research?
The growing interest in the molecular subclassification of colorectal cancers is increasingly facilitated by large multicenter biobanking initiatives. The quality of tissue sampling is pivotal for successful translational research. This study shows the quality of fresh frozen tissue sampling within a multicenter cohort study for colorectal cancer (CRC) patients. Each of the seven participating hospitals randomly contributed ten tissue samples, which were collected following Standard Operating Procedures (SOP) using established techniques. To indicate if the amount of intact RNA is sufficient for molecular discovery research and prove SOP compliance, the RNA integrity number (RIN) was determined. Samples with a RIN < 6 were measured a second time and when consistently low a third time. The highest RIN was used for further analysis. 91% of the tissue samples had a RIN ≥ 6 (91%). The remaining six samples had a RIN between 5 and 6 (4.5%) or lower than 5 (4.5%). The median overall RIN was 7.3 (range 2.9-9.0). The median RIN of samples in the university hospital homing the biobank was 7.7 and the median RIN for the teaching hospitals was 7.3, ranging from 6.5 to 7.8. No differences were found in the outcome of different hospitals (p = 0.39). This study shows that the collection of high quality fresh frozen samples of colorectal cancers is feasible in a multicenter design with complete SOP adherence. Thus, using basic sampling techniques large patient cohorts can be organized for predictive and prognostic (bio)marker research for CRC.


Glomerulonephritis in children with mixed connective tissue disease.
Mixed connective tissue disease (MCTD) has overlapping clinical features with systemic lupus erythematosus (SLE). Renal biopsy is necessary for all children with SLE to evaluate the prognosis, because they are at a quite high risk of developing renal complications. Furthermore, lupus nephritis and hypocomplementemia usually precede the appearance of clinical manifestations. Immune complex-mediated nephritis is one of the major complications of MCTD. Juvenile MCTD is known to be associated with a higher risk of nephritis than adult MCTD. However, it is uncertain whether all children with MCTD should be subjected to a renal biopsy, and whether most of those with hypocomplementemia present nephropathy, as in patients with SLE. We examined the histopathological characteristics of juvenile MCTD nephritis, the importance of renal biopsy and the implications of hypocomplementemia in our patients and reported cases of MCTD. We performed renal biopsy in 11 children with MCTD and found 6 patients with glomerulonephritis. In addition, we studied the frequency and the characteristics of glomerulonephritis in 71 cases of juvenile MCTD (our 11 patients and 60 reported cases). We also analyzed the relationship between hypocomplementemia and pathological features in 41 cases of MCTD nephritis (23 adults, 18 children). 6 of our 11 patients had glomerulonephritis, but of them four had no abnormality in urinalysis at the time of biopsy. In 5 patients renal biopsy showed normal findings. Review of 71 cases of juvenile MCTD showed that of them 28% presented latent asymptomatic nephritis at the time of biopsy. Membranous nephropathy (MN) and mesangial proliferative glomerulonephritis (MPG) were common in MCTD. Interestingly, hypocomplementemia was more frequently observed in patients with MN or mixed form of MN and MPG (MPG/MN) than simple MPG based on our review of 41 cases (p < 0.01). A more aggressive indication of renal biopsy should be considered in children with MCTD because of the high incidence of non-clinical nephritis. The hypocomplementemia observed in patients with MCTD suggests the high frequency of glomerulonephritis, including membranous lesions.


A Binder Jet Printed, Stainless Steel Preconcentrator as an In-Line Injector of Volatile Organic Compounds.
A conventional approach to making miniature or microscale gas chromatography (GC) components relies on silicon as a base material and MEMS fabrication as manufacturing processes. However, these devices often fail in medium-to-high temperature applications due to a lack of robust fluidic interconnects and a high-yield bonding process. This paper explores the feasibility of using metal additive manufacturing (AM), which is also known as metal 3D printing, as an alternative platform to produce small-scale microfluidic devices that can operate at a temperature higher than that which polymers can withstand. Binder jet printing (BJP), one of the metal AM processes, was utilized to make stainless steel (SS) preconcentrators (PCs) with submillimeter internal features. PCs can increase the concentration of gaseous analytes or serve as an inline injector for GC or gas sensor applications. Normally, parts printed by BJP are highly porous and thus often infiltrated with low melting point metal. By adding to SS316 powder sintering additives such as boron nitride (BN), which reduces the liquidus line temperature, we produce near full-density SS PCs at sintering temperatures much lower than the SS melting temperature, and importantly without any measurable shape distortion. Conversely, the SS PC without BN remains porous after the sintering process and unsuitable for fluidic applications. Since the SS parts, unlike Si, are compatible with machining, they can be modified to work with commercial compression fitting. The PC structures as well as the connection with the fitting are leak-free with relatively high operating pressures. A flexible membrane heater along with a resistance-temperature detector is integrated with the SS PCs for thermal desorption. The proof-of-concept experiment demonstrates that the SS PC can preconcentrate and inject 0.6% headspace toluene to enhance the detector's response.


Chitosan-mediated and spatially selective electrodeposition of nanoscale particles.
Nanoscale particles offer a variety of interesting properties, and there is growing interest in their assembly into higher ordered structures. We report that the pH-responsive aminopolysaccharide chitosan can mediate the electrodeposition of model nanoparticles. Chitosan is known to electrodeposit at the cathode surface in response to a high localized pH. To demonstrate that chitosan can mediate nanoparticle deposition, we suspended fluorescently labeled latex nanoparticles (100 nm diameter spheres) in a chitosan solution (1%) and performed electrodeposition (0.05 mA/cm2 for several minutes). Results demonstrate that chitosan is required for nanoparticle electrodeposition; chitosan confers spatial selectivity to electrodeposition; and nanoparticles distribute throughout the electrodeposited chitosan film. Additionally, we observed that the deposited films reversibly swell upon rehydration. This work indicates that chitosan provides a simple means to assemble nanoparticles at addressable locations and provides further evidence that stimuli-responsive biological materials may facilitate fabrication at the microscale.


Quantitative assessment of T cell repertoire recovery after hematopoietic stem cell transplantation.
Delayed T cell recovery and restricted T cell receptor (TCR) diversity after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are associated with increased risks of infection and cancer relapse. Technical challenges have limited faithful measurement of TCR diversity after allo-HSCT. Here we combined 5' rapid amplification of complementary DNA ends PCR with deep sequencing to quantify TCR diversity in 28 recipients of allo-HSCT using a single oligonucleotide pair. Analysis of duplicate blood samples confirmed that we accurately determined the frequency of individual TCRs. After 6 months, cord blood-graft recipients approximated the TCR diversity of healthy individuals, whereas recipients of T cell-depleted peripheral-blood stem cell grafts had 28-fold and 14-fold lower CD4(+) and CD8(+) T cell diversities, respectively. After 12 months, these deficiencies had improved for the CD4(+) but not the CD8(+) T cell compartment. Overall, this method provides unprecedented views of T cell repertoire recovery after allo-HSCT and may identify patients at high risk of infection or relapse.


Application of Near-infrared Light Transillumination in Restorative Dentistry: A Review.
This paper presents the various applications of near-infrared light transillumination (NILT) in dentistry. Untreated dental caries is considered the most prevalent health condition affecting both children and adults worldwide. Increased awareness and a paradigm shift toward utilization of minimally invasive treatment procedures and nonionizing radiation led to the discovery of newer techniques for screening and early diagnosis of demineralized lesions. Demineralized lesions detected early can be treated with minimally invasive treatment procedures such as the usage of fluoridated dentifrice to encourage remineralization and resin infiltration to arrest caries progression. NILT procedure involves noninvasive, nonionizing radiation and helps in the identification of early demineralized lesions using light transillumination. At near-infrared wavelengths, the enamel appears translucent and helps in visualizing and detecting demineralized lesions when long-wave light transilluminated against the tooth surface. The wavelength in the range of 1310 nm is considered best for the transillumination of lesions. This technique has been proven to be successful in the detection of carious and demineralized lesions. NILT can be used as a screening tool for the early detection of demineralized lesions and can be considered as an adjunct to bitewing radiographs. It can be advantageous in screening pregnant, growing adolescent patients and in cases where multiple follow-ups are needed and ionizing radiation must be avoided. Keywords: Dental caries, Early diagnosis, Ionizing radiation, Minimally invasive, Near-infrared, Occlusal caries, Transillumination.


Bacterial Lysates as Immunotherapies for Respiratory Infections: Methods of Preparation.
Bacterial lysates, prepared from the microorganisms most frequently involved in human Respiratory Tract Infections (RTIs) have been in the market for several decades, and at present, several different brands are available in many countries worldwide. They all claimed to exert local and systemic immunomodulatory effects but different clinical trials show disparate results between them. The lack of consistency of predicted therapeutic effects has undermined their clinical use and hampered licensing in several countries. One explanation for such lack of consistency in the results is that their methods of preparation are also very different. Here, we review the available literature describing methods of preparation of bacterial lysates, including patent disclosure documents. We found a great variety of methodologies of preparation and a lack of standardized procedures among them. The main conclusion of our study is that there is a clear need for standardized protocols of production to obtain comparable results in clinical trials worldwide.


Arousal-based scoring of obstructive hypopneas.
Obstructive sleep apnea in adults is diagnosed by an apnea-hypopnea index (AHI) above five (at least five apneas and/or hypopneas per hour of sleep). Though the definition of apneas has remained stable, the scoring criteria for hypopneas has varied throughout the years. There is even more evidence now that scoring respiratory events associated with arousals should be included in the diagnosis of obstructive sleep apnea, as these patients may benefit from treatment. Recent studies, trials and meta-analyses have demonstrated that respiratory events associated with arousal are associated with symptoms, such as poor sleep quality and excessive daytime sleepiness. These arousal-based hypopneas have also been noted to carry a risk of hypertension and other adverse health consequences. Requiring a 4% oxygen desaturation for hypopneas may miss patients that may benefit from treatment for obstructive sleep apnea. These patients are typically younger, nonobese, and women as they have been found to have respiratory events causing sleep fragmentation versus significant oxygen desaturation as compared with other populations.


Diminished retention of food in the proximal stomach correlates with increased acidic reflux in patients with gastroesophageal reflux disease and dyspeptic symptoms.
This work aimed at evaluating the intragastric distribution of food in patients with GERD and dyspepsia and its relationship to acidic reflux episodes. Gastric emptying and food retention in the proximal stomach were evaluated by scintigraphy in 12 healthy subjects and 19 patients with GERD and dyspepsia after a liquid test meal. Patients also underwent 24-hr esophageal pH monitoring, which included a 2-hr postprandial period following a similar test meal. Total gastric emptying was similar in patients and controls, whereas proximal gastric retention (AUCprox/AUCtot) was significantly decreased in patients (mean +/- SD: 0.48 +/- 0.07 vs. 0.56 +/- 0.06; P = 0.02). Within the GERD-dyspepsia group, a significant negative correlation was found between proximal gastric retention and the number of acidic reflux episodes. We concluded that abnormally decreased retention of gastric contents in the proximal stomach after a liquid meal may contribute to the pathogenesis of acidic reflux episodes in patients with GERD and dyspepsia.


Detection and Molecular Characterization of Escherichia coli Strains Producers of Extended-Spectrum and CMY-2 Type Beta-Lactamases, Isolated from Turtles in Mexico.
Multidrug-resistant bacteria are a growing problem in different environments and hosts, but scarce information exists about their prevalence in reptiles. The aim of this study was to analyze the resistance mechanisms, molecular typing, and plasmid content of cefotaxime-resistant (CTX(R)) Escherichia coli isolates recovered from cloacal samples of 71 turtles sheltered in a herpetarium in Mexico. CTX(R)-E. coli were recovered in 11 of 71 samples (15.5%), and one isolate/sample was characterized. Extended-spectrum β-lactamase (ESBL)-producing E. coli isolates were detected in four samples (5.6%): two strains carried the blaCTX-M-2 gene (phylogroup D and ST2732) and two contained the blaCTX-M-15 gene (phylogroup B1 and lineages ST58 and ST156). The blaCMY-2 gene was detected by PCR in E. coli isolates of eight samples (9.8%) (one of them also carried blaCTX-M-2); these isolates were distributed into phylogroups A (n = 1), B1 (n = 6), and D (n = 1) and typed as ST155, ST156, ST2329, and ST2732. Plasmid-mediated quinolone resistance (PMQR) genes were detected in five isolates [aac(6')Ib-cr, qnrA, qnrB19, and oqxB]. From three to five replicon plasmids were detected among the strains, being IncFIB, IncI1, IncFrep, and IncK the most prevalent. ESBL or pAmpC genes were transferred by conjugation in four strains, and the blaCTX-M-15 and blaCMY-2 genes were localized in IncFIB or IncI1 plasmids by Southern blot hybridization assays. Class 1 and/or class 2 integrons were detected in eight strains with six different structures of gene cassette arrays. Nine pulsed-field gel electrophoresis patterns were found among the 11 studied strains. To our knowledge, this is the first detection of ESBL, CMY-2, PMQR, and mobile determinants of antimicrobial resistance in E. coli of turtle origin, highlighting the potential dissemination of multidrug-resistant bacteria from these animals to other environments and hosts, including humans.


Microsatellites mapping for non-model species with chromosomal rearrangement: a case study in the frog Quasipaa boulengeri (Anura: Dicroglossidae).
Gene mapping is an important resource for understanding the evolution of genes and cytogenetics. Model species with a known genetic map or genome sequence allow for the selection of genetic markers on a desired chromosome, while it is hard to locate these markers on chromosomes of non-model species without such references. A frog species, Quasipaa boulengeri, shows chromosomal rearrangement polymorphisms, making itself a fascinating model for chromosomal speciation mediated by suppressed recombination. However, no markers have been located on its rearranged chromosomes. We present a complete protocol to map microsatellites based on mechanical microdissection and chromosome amplification techniques. Following this protocol, we mapped 71 microsatellites of Q. boulengeri at the chromosome level. In total, eight loci were assigned to rearranged chromosomes, and the other 63 loci might attach to other chromosomes. These microsatellites could be used to compare the gene flow and verify the chromosomal suppressed recombination hypothesis in Q. boulengeri. This integrated protocol could be effectively used to map genes to chromosomes for non-model species.


Within-Body Distributions and Feeding Effects of the Neonicotinoid Insecticide Clothianidin in Bumblebees (Bombus terrestris).
Bumblebees can be exposed to neonicotinoid pesticides through nectar and pollen collected from treated crops, which can cause lethal and sublethal effects in these nontarget pollinators. However, the body distribution of the compound after exposure to neonicotinoids in bumblebees is not well studied. Bumblebee colonies (Bombus terrestris, n = 20) were exposed to field-realistic concentrations of clothianidin through artificial nectar (3.6-13 µg/L) for 9 d. Comparison of the nominal with the measured exposure in nectar indicated good compliance, confirming the applicability of the method. When quantified, clothianidin showed a concentration-dependent occurrence in the head and body of workers (head: <0.2-2.17 µg/kg; body: <0.2-3.17 µg/kg), and in the body of queens (<0.2-2.49 µg/kg), although concentrations were below those measured in the nectar (bioaccumulation factor = 0.2). Exposure to clothianidin did not affect mortality nor brood production, nor did it have a statistically significant effect on nectar consumption and size of food storage. However, visual inspection suggests higher nectar consumption of nectar with low clothianidin content compared with nectar with no or high clothianidin content. Our results show that dietary clothianidin is taken up in bumblebees, but does not bioaccumulate to elevated levels compared with exposure. Still, clothianidin may elicit responses that affect feeding behavior of the pollinator B. terrestris, although our endpoints were not significantly affected. Environ Toxicol Chem 2021;40:2781-2790. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.


A pilot randomised controlled study of the mental health first aid eLearning course with UK medical students.
Medical students face many barriers to seeking out professional help for their mental health, including stigma relating to mental illness, and often prefer to seek support and advice from fellow students. Improving medical students' mental health literacy and abilities to support someone experiencing a mental health problem could reduce barriers to help seeking and improve mental health in this population. Mental Health First Aid (MHFA) is an evidence-based intervention designed to improve mental health literacy and ability to respond to someone with a mental health problem. This pilot randomised controlled trial aims to evaluate the MHFA eLearning course in UK medical students. Fifty-five medical students were randomised to receive six weeks access to the MHFA eLearning course (n = 27) or to a no-access control group (n = 28). Both groups completed baseline (pre-randomisation) and follow-up (six weeks post-randomisation) online questionnaires measuring recognition of a mental health problem, mental health first aid intentions, confidence to help a friend experiencing a mental health problem, and stigmatising attitudes. Course feedback was gathered at follow-up. More participants were lost follow-up in the MHFA group (51.9%) compared to control (21.4%). Both intention-to-treat (ITT) and non-ITT analyses showed that the MHFA intervention improved mental health first aid intentions (p = <.001) and decreased stigmatising attitudes towards people with mental health problems (p = .04). While ITT analysis found no significant Group x Time interaction for confidence to help a friend, the non-ITT analysis did show the intervention improved confidence to help a friend with mental health problems (p = <.001), and improved mental health knowledge (p = .003). Medical students in the intervention group reported a greater number of actual mental health first aid actions at follow-up (p = .006). Feedback about the MHFA course was generally positive, with participants stating it helped improve their knowledge and confidence to help someone. This pilot study demonstrated the potential for the MHFA eLearning course to improve UK medical students' mental health first aid skills, confidence to help a friend and stigmatising attitudes. It could be useful in supporting their own and others' mental health while studying and in their future healthcare careers. Retrospectively registered ( ISRCTN11219848 ).


Hurry up, it's quiet in the emergency department.
Emergency department (ED) crowding is a contemporary problem. Solutions are multiple, but often involve a lengthy implementation process and/or substantial funding. Therefore, it is important that in the meanwhile, we aim to identify simple strategies, focussing on optimising efficiency of the available resources, which can be adopted in the ED here and now. We made a careful analysis of inflow, throughput and outflow data of all 24,823 patients visiting the ED of a large teaching hospital in the year 2015, and looked in more detail at the 10 days with the longest average throughput times. The average throughput time during the study period was 130 minutes. The time between inflow and outflow peaks was well beyond the average daily ED throughput time, indicating that the 'midday surge in patient arrivals could not be handled adequately by the ED system. For the 10 days with the longest average throughput times, we found a very distinctive pattern, with a backlog of patients building up in the morning hours when maximum bed capacity had not yet been reached. This backlog had consequences during a significant part of the day. Improved timing of internal efforts in the ED based on careful analysis of ED performance data should be an integral part of a system approach to prevent ED crowding.


Domains of interaction between alpha interferon and its receptor components.
We describe how constraints on the binding of human interferons (IFNs), alpha1 and alpha2 and alpha8 on mouse cells are partially relieved by the expression of the bovine (Bo) or human (Hu) IFN alpha/beta receptor (IFNAR) component in these cells. We show that, while the binding of all three is substantially increased by the transfection of Bo IFNAR, it is accompanied by an increase in activity only in the case of alpha2 and alpha8 (IFNs that otherwise have little activity on mouse cells). IFN alpha1, which shows some partial activity on mouse cells, responds to the presence of Bo IFNAR by acting, at low concentrations, as a competitive antagonist to IFNs alpha2 and alpha8. A review of published results on IFN hybrid scanning and on the effects of expressing Bo IFNAR in human cells led us to propose that an N-terminal segment of the IFN molecule interacts directly with IFNAR. Applying site-directed mutagenesis to an IFN hybrid; alpha8[60]alpha1[92]alpha8, we show that the point mutations K84 to E84 and Y90 to D90 act synergistically to cause the hybrid to behave as the parental IFN alpha8, switching the preference from Mu to Hu IFNAR in transfected mouse cells. The published structural models for IFN reveal that positions 84 and 90 span the exposed residues of the alpha-helix C of the IFN molecule. We derive a model of IFN-receptor interaction in which the A helix and the C helix of IFN interact with IFNAR and in which a binding phase can be distinguished from a binding/activity phase. We propose that the so-called "hot" domains of the IFN molecule (the AB loop and the D helix) are presented by IFNAR to interact with an additional component of the functional receptor.


Initial stage of transformation of permissive cells by simian virus 40: development of resistance to productive infection.
A quantitative assay has been used to determine the conditions leading to acquisition of resistance of permissive cells to lytic infection. The number of cell colonies surviving infection depends on the occurrence of several cell divisions after infection. High yields of resistant colonies were obtained when infected, confluent cultures were released from contact inhibition 10 to 14 hr after infection. Infection of actively growing cells produced similar results, but halting further division by seeding these growing cells on confluent monolayers prevented the development of colonies. Colony formation was a direct function of multiplicities lower than 5. An inverse killing response was observed with higher multiplicities, yet colonies were produced at a multiplicity of infection as high as 50. Brief exposure of input simian virus 40 to ultraviolet light stimulated colony formation. Irradiation of the virus for longer periods of time led to reduction of colony formation at a rate slower than the rate of inactivation of viral infectivity. It was concluded that resistance is induced by simian virus 40 and that this alteration represents one of the earliest detectable characteristics of the transformation of permissive cells.


Quinazoline and quinazolinone as important medicinal scaffolds: a comparative patent review (2011-2016).
Quinazoline and quinazolinone scaffolds represent an important class of biologically active nitrogen heterocyclic compounds. A variety of marketed drugs are based on these moieties. A diverse range of molecules with quinazoline/quinazolinone moieties have been reported to exhibit broad spectrum of biological activities. This review covers recent efforts in the synthesis and biological screening of quinazoline/quinazolinone based compounds from 2011-2016. Quinazoline and quinazolinones represent a diverse class of biologically active nitrogen heterocyclic compounds with immense therapeutic potential. Their ease of synthetic accessibility, and flexibility in structural modifications and functionalization further adds to their appeal in medicinal chemistry. A number of currently available drugs are based on quinazoline/quinazolinone scaffold. It is interesting to note that, among the recent patents available, a lot of them focus on the promising anticancer activity of quinazoline and quinazolinone containing compounds. However their biological activity is certainly not limited to anticancer only, they are also known to elicit a number of other biological and physiological effects in vitro and in vivo respectively. The interest in quinazolines and quinazolinones is ever growing, since they offer a fairly diverse chemical space for exploration of medicinal potential.


Comparison of Recharge Estimation Methods During a Wet Period in a Karst Aquifer.
Management of water resources, implying their appropriate protection, calls for a sound evaluation of recharge. Such assessment is very complex in karst aquifers. Most methods are developed for application to detrital aquifers, without taking into account the extraordinary heterogeneity of porosity and permeability of karst systems. It is commonly recommended to estimate recharge using multiple methods; however, differences inherent to the diverse methods make it difficult to clarify the accuracy of each result. In this study, recharge was estimated in a karst aquifer working in a natural regime, in a Mediterranean-type climate, in the western part of the Sierra de las Nieves (southern Spain). Mediterranean climate regions are characterized by high inter-annual rainfall variability featuring long dry periods and short intense wet periods, the latter constituting the most important contribution to aquifer water input. This paper aims to identify the methods that provide the most plausible range of recharge rate during wet periods. Six methods were tested: the classical method of Thornthwaite-Mather, the Visual Balan code, the chloride balance method, and spatially distributed methods such as APLIS, a novel spatiotemporal estimation of recharge, and ZOODRM. The results help determine valid methods for application in the rest of the unit of study and in similar karst aquifers.


Millimeter wave absorption spectra of biological samples.
A solid-state computer-controlled system has been used to make swept-frequency measurements of absorption of biological specimens from 26.5 to 90.0 GHz. A wide range of samples was used, including solutions of DNA and RNA, and suspensions of BHK-21/C13 cells, Candida albicans, C krusei, and Escherichia coli. Sharp spectra reported by other workers were not observed. The strong absorbance of water (10--30 dB/mm) caused the absorbance of all aqueous preparations that we examined to have a water-like dependence on frequency. Reduction of incident power (to below 1.0 microW), elimination of modulation, and control of temperature to assure cell viability were not found to significantly alter the water-dominated absorbance. Frozen samples of BHK-21/C13 cells tested at dry ice and liquid nitrogen temperatures were found to have average insertion loss reduced to 0.2 dB/cm but still showed no reproducible peaks that could be attributed to absorption spectra. It is concluded that the special resonances reported by others are likely to be in error.


T-lymphocytes subpopulation before and after surgical removal of hepatocellular carcinoma.
This study included 16 histologically confirmed hepato-cellular carcinoma (HCC) patients. At the same time, 32 normal healthy individuals and 20 asymptomatic hepatitis B surface antigen (HBsAg) carriers were served as control groups. The study disclosed that T cells, OKT4 cells and the ratio of OKT4 cells/OKT8 cells in peripheral venous blood of HCC patients before surgery were lower than that of either normal control or asymptomatic HBsAg carriers. The difference was statistically significant. The T cells, OKT4 cells and the ratio of OKT4 cells/OKT8 cells of 4 HCC patients with positive HBeAg did not show further decrease as compared with that of 12 HCC patients with negative HBeAg. Periodic examination of T cells, OKT4 cells and OKT8 cells in 16 HCC patients after surgical removal of hepatocellular carcinoma tumor revealed that preoperative depressed T cells will decline further in the first postoperative week, but it will gradually increase to near normal range in the fourth or fifth postoperative week. However, OKT4 cells still remained in depressed state during the postoperative observation period. In the conclusion, it has been suggested that the derangement of T-cell subsets observed in HCC patients is not related to either HBsAg or even HBeAg. It can be either precondition to HCC formation or further follow up period being needed to look for the change of OKT4 cells.


Vigabatrin inhibits seizures and mTOR pathway activation in a mouse model of tuberous sclerosis complex.
Epilepsy is a common neurological disorder and cause of significant morbidity and mortality. Although antiseizure medication is the first-line treatment for epilepsy, currently available medications are ineffective in a significant percentage of patients and have not clearly been demonstrated to have disease-specific effects for epilepsy. While seizures are usually intractable to medication in tuberous sclerosis complex (TSC), a common genetic cause of epilepsy, vigabatrin appears to have unique efficacy for epilepsy in TSC. While vigabatrin increases gamma-aminobutyric acid (GABA) levels, the precise mechanism of action of vigabatrin in TSC is not known. In this study, we investigated the effects of vigabatrin on epilepsy in a knock-out mouse model of TSC and tested the novel hypothesis that vigabatrin inhibits the mammalian target of rapamycin (mTOR) pathway, a key signaling pathway that is dysregulated in TSC. We found that vigabatrin caused a modest increase in brain GABA levels and inhibited seizures in the mouse model of TSC. Furthermore, vigabatrin partially inhibited mTOR pathway activity and glial proliferation in the knock-out mice in vivo, as well as reduced mTOR pathway activation in cultured astrocytes from both knock-out and control mice. This study identifies a potential novel mechanism of action of an antiseizure medication involving the mTOR pathway, which may account for the unique efficacy of this drug for a genetic epilepsy.


Social Cognition in Schizophrenia Patients and Their First-Degree Relatives.
Social cognition is a person's ability to configure the designs of relationships between themselves and others and to use these designs to guide social behaviors in a flexible manner. The models that are the most studied and describe social cognition are the theory of mind (ToM) and emotion recognition. This study was aimed to detect ToM and emotion recognition disorders in schizophrenia patients and their first-degree relatives. Thirty schizophrenia patients in remission, the first-degree relatives of schizophrenia patients (n=30), and 30 healthy volunteers who were paired with the patients in terms of age and duration of education were included in the study. The Positive and Negative Symptom Scale (PANSS), Dokuz-Eylül Theory of Mind Scale (DEToMS), Reading the Mind in the Eyes test, Facial Emotion Identification Test (FEIT), and Facial Emotion Discrimination Test (FEDT) were performed by the patients participating in this study. ToM and emotion recognition were found to be defective in the schizophrenia patients and their relatives. The performances of ToM and emotion recognition were ranked as the schizophrenia group, family group, and control group, from the worst to the best. The schizophrenia group showed poor performance in all sub-components except irony. In the family group, the empathy subcomponent showed similar performance with the control group, whereas the subcomponents of the second-order false belief, metaphor, and faux pas tests showed similar performance with the patient group. There were differences among the three groups in the first-order false belief subscale as well as the total DEToMS. The patient and family groups showed the poorest performances, whereas the control group showed the best performance. The detection of ToM and emotion recognition disorders in the remission period, regardless of the attack period and asymptomatic first-degree relatives, may support the view that the period of schizophrenia is an independent continuous variable.


Compartments in arteriovenous malformation nidi demonstrated with rotational three-dimensional digital subtraction angiography by using selective microcatheterization. Report of three cases.
Although in several histological studies of arteriovenous malformation (AVM) nidi the presence of compartments has been documented, no clinical study has been published. The present study was conducted to determine the presence of nidus compartments in clinical cases by using a new radiographic method. Two patients with unruptured and one with a ruptured AVM (all Spetzler-Martin Grade III) were studied. A microcatheter was superselectively introduced into each of two or three feeding arteries of the AVMs under three-dimensional (3D) angiographic guidance to obtain 3D images of the nidus by using rotational digital subtraction angiography. On 3D images the different feeding arteries were found to be independent from one another, which allowed the authors to confirm the presence of compartments. On the other hand, separate feeding arteries often had a common draining vessel. Compartments in AVM nidi were demonstrated by a novel rotational 3D angiographic procedure by using superselective microcatheterization, which should be useful for designing treatment strategies for large and complex AVMs.


Age and secular distributions of virus-proven influenza patients in successive epidemics 1961-1976 in Cirencester: epidemiological significance discussed.
A general practice population of around 3900, under continuous clinical and laboratory surveillance, experienced 20 outbreaks of influenza between March 1960 and March 1976. Four epidemics were caused by subtype H2N2 type A viruses, seven by subtype H3N2 type A viruses and nine outbreaks by type B viruses. The age of every person proved virologically to have influenza is related to the age structure of the community and to the phase of the epidemic in which the virus-positive specimens were collected. Children 0-15 years old suffered a higher incidence rate than adults 16-90+. Pre-school children 0-4 suffered the highest rate of infection by viruses of both influenza A subtypes, whereas older schoolchildren 10-15 suffered the highest rate of type B infections. Despite these high incidence rates neither pre-school nor schoolchildren appear to have been the major disseminators of any of these influenza viruses in the community. Adults of all ages suffered a high rate of infection even into extreme old age, and the indiscriminate age distribution among adults was sustained in the successive epidemics. Such age-patterns are not those caused by a highly infectious immunizing virus surviving by means of direct transmissions from the sick, whose prompt development of the disease continues endless chains of transmissions. An alternative epidemic mechanism--whereby the virus does not spread from the sick but becomes latent in them, reactivating seasonally so that they later infect their companions--would produce age patterns similar to those recorded here for influenza patients. The suggested mechanism is illustrated by a simple conceptual model and the influenzal age patterns are discussed in relation to the recycling of influenza A subtypes.


Self-similar scaling in decaying numerical turbulence.
Decaying turbulence is studied numerically using as initial condition a random flow whose shell-integrated energy spectrum increases with wave number k like k(q). Alternatively, initial conditions are generated from a driven turbulence simulation by simply stopping the driving. It is known that the dependence of the decaying energy spectrum on wave number, time, and viscosity can be collapsed onto a unique scaling function that depends only on two parameters. This is confirmed using three-dimensional simulations and the dependence of the scaling function on its two arguments is determined.


Label-free MS imaging from drug discovery to preclinical development.
To fully understand the drug mechanism of action of new chemical entities, pharmacologists need to acquire confident and precise data in pharmacokinetics and in pharmacodynamics and build strong pharmacokinetic/pharmacodynamic relationships. Target engagement in evaluating new chemical entities provides the basis for treatment efficacy. Classical technologies are sometimes limited or inefficient to provide these precise data; however, label-free MS imaging technology is able to provide these molecular features, spatial distributions, quantification and metabolomics data. Important considerations for imaging biological sections are described. Various applications in pharmacology are presented across different therapeutic areas, where MS imaging answers crucial drug discovery and preclinical development needs.


Drainage-related Complications in Percutaneous Transhepatic Biliary Drainage: An Analysis Over 10 Years.
Procedure-related complications of percutaneous transhepatic biliary drainage (PTBD) have been well documented in the literature. However, relatively restricted data are available concerning drainage-related complication rates in long-term PTBD therapy. The present retrospective study evaluated the extent and the nature of drainage complications during PTBD therapy and associated risk factors for these complications. Between June 1997 and May 2007, a total of 385 patients with PTBD were identified by analyzing the PTBD database and hospital charts, with a total of 2468 percutaneous biliary drainages being identified. Among the identified patients, 243 (63%) had malignant and 142 (37%) had benign bile duct strictures. At least 1 drainage-related complication was observed in 40% of the patients. With respect to the total number of drains, prosthesis complications occurred in 23%. Occlusion, dislocation, and cholangitis were the most common complications observed during PTBD therapy. Risk factors for cholangitis and occlusion were malignant disease, prior occurrence of complications, and bilateral drainage. Proximal stenosis of the biliary system was close to significant. Drainage-related complications are a major problem in PTBD therapy. The risk factors for occlusion and cholangitis discovered in this study can help to refine individual strategies to reduce the rate of these drainage complications.


Extracellular matrix recovery by human articular chondrocytes after treatment with hyaluronan hexasaccharides or Streptomyces hyaluronidase.
Abstract The treatment of human articular chondrocytes with Streptomyces hyaluronidase (St-HA'ase) or hyaluronan hexasaccharides (HA6) provides two approaches to the selective depletion of specific components of the extracellular matrix, and an opportunity to follow the reparative responses initiated by these changes. In this study, changes in the relative expression of messenger RNA for hyaluronan synthase-2, CD44, and aggrecan were determined by competitive, quantitative reverse transcriptase-polymerase chain reaction. Changes in the size of the cell-associated matrix surrounding live chondrocytes were analyzed by the particle exclusion assay, and hyaluronan accumulation was characterized using a biotin-labeled hyaluronan-specific binding protein. Both Streptomyces hyaluronidase as well as hyaluronan hexasaccharide treatment of chondrocytes resulted in an approximately 2-fold increase in hyaluronan synthase-2 mRNA copy numbers, together with a 1.8-fold increase in the mRNA copy number for the proteoglycan aggrecan. However, although matrix biosynthesis was enhanced, the chondrocytes failed to retain these components. Both treatments resulted in a diminished accumulation of extracellular hyaluronan as well as a loss of the chondrocyte proteoglycan-rich cell-associated matrix. Thus, this model is similar to the early stages of osteoarthritis. Upon removal of the Streptomyces hyaluronidase or hyaluronan hexasaccharides, the normal, healthy, adult human chondrocytes used in this study regained their capacity to retain extracellular hyaluronan and to reassemble and retain a cell-associated matrix. This stimulation of hyaluronan synthase-2 (HAS-2) and aggrecan mRNA expression, and the subsequent capacity to retain the newly synthesized extracellular matrix, illustrate the events which are necessary for adult human articular chondrocytes to undergo effective repair.


Subacromial impingement in patients with whiplash injury to the cervical spine.
Impingement syndrome and shoulder pain have been reported to occur in a proportion of patients following whiplash injuries to the neck. In this study we aim to examine these findings to establish the association between subacromial impingement and whiplash injuries to the cervical spine. We examined 220 patients who had presented to the senior author for a medico-legal report following a whiplash injury to the neck. All patients were assessed for clinical evidence of subacromial impingement. 56/220 patients (26%) had developed shoulder pain following the injury; of these, 11/220 (5%) had clinical evidence of impingement syndrome. Only 3/11 patients (27%) had the diagnosis made prior to evaluation for their medico-legal report. In the majority, other clinicians had overlooked the diagnosis. The seatbelt shoulder was involved in 83% of cases (p < 0.03). After a neck injury a significant proportion of patients present with shoulder pain, some of whom have treatable shoulder pathology such as impingement syndrome. The diagnosis is, however, frequently overlooked and shoulder pain is attributed to pain radiating from the neck resulting in long delays before treatment. It is important that this is appreciated and patients are specifically examined for signs of subacromial impingement after whiplash injuries to the neck. Direct seatbelt trauma to the shoulder is one possible explanation for its aetiology.


Primary structures of Escherichia coli pyruvate formate-lyase and pyruvate-formate-lyase-activating enzyme deduced from the DNA nucleotide sequences.
The structural gene of pyruvate formate-lyase (pfl) and that of pyruvate-formate-lyase-activating enzyme were shown to be adjacent on the chromosomal map of Escherichia coli. DNA sequencing was performed along a stretch of 3592 nucleotides to obtain the amino acid sequences of both proteins. The derived primary structures (759 and 245 residues) were confirmed by partial structure analyses on the purified proteins. The open reading frames are separated by a 194-nucleotide stretch, and their flanking regions include signal elements that are compatible with separate control of protein synthesis from the two genes.


Blood pressure changes after catheter-based renal denervation are related to reductions in total peripheral resistance.
Renal denervation (RDN) can reduce sympathetic activity and blood pressure (BP) in patients with uncontrolled hypertension. The exact mechanisms by which RDN results in BP reductions are yet not fully established. This study investigated the effects of RDN on office BP, 24-h ambulatory BP, noninvasive 10-min beat-to-beat digital pulse wave analysis, total peripheral resistance (TPR), cardiac output, and plasma renin and aldosterone serum concentrations in 30 patients with resistant hypertension. Adherence to antihypertensive drugs was assessed by liquid chromatography high-resolution tandem mass spectrometry analysis in plasma and urine at baseline and at 6 month. RDN significantly reduced office BP, beat-to-beat BP, and 24-h ambulatory BP by 19/6 (P = 0.021/P = 0.012), 12/7 (P = 0.005/P = 0.005), and 10/5 mmHg (P = 0.001/P = 0.049) at 6 months, respectively. TPR decreased from 1696 to 1377 dyn × s/cm (-19%; P = 0.027). This reduction was not associated with significant changes in cardiac output. The changes in office, ambulatory, and beat-to-beat BP correlated with the reductions of TPR. Adherence to antihypertensive treatment remained unchanged during the study period (84.7% at baseline, 83.6% at 6 months, P = 0.782). RDN reduced office BP, beat-to-beat BP, and 24-h ambulatory BP in patients with resistant hypertension after 6 months. The BP changes were associated with reductions in peripheral resistance, whereas cardiac output, plasma renin, and aldosterone levels remained unchanged. The observed effects were not explained by an increased intake of antihypertensive medications.


Effects of tunicamycin and various monosaccharides on phytohaemagglutinin-induced autorosette formation.
The structural characteristics of autologous red blood cell (ARBC) receptors on human peripheral blood lymphocytes (PBL) induced by phytohaemagglutinin (PHA) were examined. Tunicamycin, which is known to be a blocker of the protein glycosylation of N-glycosidic type glycoprotein, significantly inhibited the production of ARBC receptors. When trypsinized PBL were cultured in the presence of tunicamycin, the inhibitory effect was enhanced. When several monosaccharides were added to the mixture of ARBC and PBL pre-treated with PHA for 24 h, D-mannose caused the most inhibition, and galactose and D-fucose also caused significant inhibition. These data suggest that N-glycosidic type glycoproteins play an important role in binding sites to ARBC on PBL surface membranes and that more than one type of glycose may be involved.


[Screening of high-risk group with colorectal cancer].
To measure the rate of high-risk group and the detection rate of colorectal cancer (CRC) in communities in Guangdong province and to provide scientific rationales for formulating mass screening plans in high-risk group. Mass survey was conducted by questionnaire combined fecal occult blood test (FOBT) in Huizhou region, Guangdong Province, to sort out the high-risk population of CRC. Then the high-risk population was screened by colonoscopy and pathology to identify CRC. The differences were compared by direct expenditure which was used to calculate screening cost. A total of 68,953 people were surveyed. There were 940 people in high-risk group (detection rate: 1.36%), 3118 in immunity FOBT positive group (detection rate: 4.52%), Merging aforementioned two groups, there were 3870 in population at risk (detection rate: 5.61%). The CRC detection rate in high-risk group, immunity FOBT positive group, population at risk and average-risk group was 506.3/10(5), 314.3/10(5), 315.9/10(5) and 17.7/10(5) respectively. The positive predictive value of CRC screening scheme by high-risk group questionnaire-colonoscopy was 0.43% while CRC screening scheme by FOBT-colonoscopy 0.22%. In terms of direct expenditure of CRC per case in high-risk group and immunity FOBT positive group was 47,834.5 yuan and 82,303.6 yuan. The latter was 1.7 times than that of the former. The scheme of questionnaire combined FOBT for CRC is an effective way in mass survey. The scheme by high-risk group questionnaire-colonoscopy has a much better cost-effectiveness than that of the scheme by FOBT-colonoscopy so that it should be one of the preferred methods for individual screening in high-risk group.


A Systematic Evaluation of the N-F Bond Strength of Electrophilic N-F Reagents: Hints for Atomic Fluorine Donating Ability.
The recent discovery of the radical reactivity of a few traditionally electrophilic N-F reagents has sparked a renaissance of radical fluorination. A knowledge of the N-F bond dissociation enthalpies (BDE) of electrophilic N-F reagents is essential for understanding of their reactivities. However, a thorough literature survey revealed that such information is extremely sparse. This prompted us to carry out the first systematic computation on the N-F BDEs of electrophilic N-F reagents. The calculated N-F BDE scale of 88 electrophilic N-F reagents ranges from 49.3 to 80.0 kcal mol-1 in acetonitrile. The large variety of N-F reagents and wide span of N-F BDEs make the scale a useful tool not only for the future rational design of novel reagents but also for judicious selection of appropriate ones to explore new radical fluorinations.


Small-scale spatial heterogeneity of arbuscular mycorrhizal fungal abundance and community composition in a wetland plant community.
Although it has become increasingly clear that arbuscular mycorrhizal fungi (AMF) play important roles in population, community, and ecosystem ecology, there is limited information on the spatial structure of the community composition of AMF in the field. We assessed small-scale spatial variation in the abundance and molecular diversity of AMF in a calcareous fen, where strong underlying environmental gradients such as depth to water table may influence AMF. Throughout an intensively sampled 2 x 2 m plot, we assessed AMF inoculum potential at a depth of 0-6 and 6-12 cm and molecular diversity of the AMF community using terminal restriction fragment length polymorphism of 18S rDNA. Inoculum potential was only significantly spatially autocorrelated at a depth of 6-12 cm and was significantly positively correlated with depth to water table at both depths. Molecular diversity of the AMF community was highly variable within the plot, ranging from 2-14 terminal restriction fragments (T-RFs) per core, but the number of T-RFs did not relate to water table or plant species richness. Plant community composition was spatially autocorrelated at small scales, but AMF community composition showed no significant spatial autocorrelation. Saturated soils of calcareous fens contain many infective AMF propagules and the abundance and diversity of AMF inoculum is patchy over small spatial scales.


A theoretical analysis of the free-energy profile of the different pathways in the alkaline hydrolysis of methyl formate in aqueous solution.
The free-energy profile for the different reaction pathways available to the hydroxide ion and methyl formate in aqueous solution is reported for the first time. The theoretical analysis was carried out by using the cluster-continuum method recently proposed by us for calculating the free energy of solvation of ions. Unlike the gas-phase reaction, our results are consistent with the fact that the reaction occurs mainly by nucleophilic attack of the hydroxide on the carbonyl carbon to yield a tetrahedral intermediate (B(AC)2 mechanism). However, an additional pathway, in which the hydroxide ion acts as a general base and a water molecule coordinated to this ion acts as the nucleophile, is also predicted to be important. The relative importance of these pathways is calculated to be 87 % and 13 %, respectively. The tetrahedral intermediate of the hydrolysis reaction has an estimated lifetime of 10 nanoseconds, and its conjugate acid has a pK(a) of 8.8. This tetrahedral intermediate is predicted to proceed to products by two pathways: elimination of methoxide ion (84 %) and by water catalyzed elimination of methanol (16 %). The less common reaction pathway, which involves attack of the hydroxide ion on the formyl hydrogen (decarbonylation mechanism) and leads to water, carbon monoxide, and methanol, is calculated to be only 3 kcal mol(-1) less favorable than the B(AC)2 mechanism. By comparison, direct attack of the hydroxide ion on the methyl group (B(AL)2 or S(N)2 mechanism) leading to an acyl-oxygen bond cleavage has a very high free energy of activation and is not expected to be important. The theoretically observed activation free energy at 298.15 K is calculated to be 15.5 kcal mol(-1), in excellent agreement with the experimentally measured value of 15.3 kcal mol(-1). This present model allows for a clear distinction between contributions due to solvation and those due to intrinsic (gas-phase) effects and proves to yield results in very good agreement with available experimental data.


A Rare Case of Levofloxacin-Induced Acute Pancreatitis: Case Report and Literature Review.
Diagnosing acute pancreatitis induced by any drug is often overlooked and warrants careful evaluation. Drug-induced acute pancreatitis is relatively rare, and diagnosis of exclusion after ruling out alcohol, gallstones, hypertriglyceridemia, and intervention. Levofloxacin, a class of fluoroquinolones, is generally recommended against various bacterial infections. While levofloxacin is mainly known for its potential side effects, such as photosensitivity and liver toxicity, it can also rarely induce acute pancreatitis. We report a case of acute pancreatitis in a female patient precipitated by levofloxacin. The patient exhibited typical manifestations of acute pancreatitis and had been taking levofloxacin for a urinary tract infection over the past three days. After ruling out other possible causes, her clinical presentation, laboratory results, and imaging findings confirmed levofloxacin-induced acute pancreatitis.


Rare clotting factor deficiency among Sudanese children.
: Rare clotting factor (F) deficiency is a deficiency of one or more of coagulation factors other than FVIII, FIX and vonWillebrand (FI, FII, FV, FV + FVIII, FVII, FIX, FX, FXI and FXIII) that cause bleeding disorders and are inherited as autosomal recessive. Descriptive study was conducted in Hemophilia Centre, Khartoum, Sudan. The medical files of pediatric patients presented to the center were reviewed retrospectively. Forty-seven patients (male : female ratio = 1.2 : 1) were included. The majority (93.6%) have parental history of consanguinity and around one third (31.9%) have family history of bleeding disorder. FV deficiency was the most common deficient factor (36.2%) followed by FI deficiency (23.4%) and FX111 deficiency (21.3%). Bruising (46.8%) and epistaxis (25.5%) were the most common presenting complains. FV deficiency mainly presented with cutaneous ecchymosis (47.1%). FI deficiency presented with umbilical bleeding (45.5%) and FXIII presented with cutaneous ecchymosis (50%). Rare clotting factor deficiency is an existing disease in Sudan with the male : female ratio was 1.2 : 1. FV deficiency, FI deficiency, FXIII deficiency were the common deficiency encountered.


[Prevalence of excess weight in preschoolers in the Northeast of Brazil].
Determine the prevalence of excess weight in preschoolers in Natal/RN and analyze the variables involved such as: gender, age, type of school (public and private) and city zones. Transversal study was performed in 20 public and 20 private schools in Natal, Brazil, between August and December, 2004. A total of 3721 children, from 2 to 6 years of age were analyzed. Children whose BMI was > or = 85 percentile were considered as excess weight and those with BMI > or = 95 percentile as overweight . Prevalence of excess weight found was 26.5% (95%CI=24.4-28.9), with 14.1% (95%CI=13.0-15.3) risk of overweight and 12.4% (95%CI=11.4-13.6) overweight. In overweight children there were more males (13.9%, 95%CI=12.4-15.6) than females (10.8%, 95%CI=9.4-12.4) (p<0.01, Prevalence ratio [PR]=1.29, 95%CI=1.08-1.53). Excess weight was found in 19.7% (95%CI=17.1-22.7) of public school students and in 32.5% (95%CI=29.3-35.9) of private school students (p<0.01, [PR]=1.64, 95%CI=1.47-1.84). Overweight prevalence was 7.1% (95%CI=6.0-8.4) and 17.1% (95%CI=15.5-18.8), respectively (p<0.01, [PR]=2.41, 95%CI=1.98-2.93). The East + South zones, areas with a better quality of life index, showed higher percentages of excess weight (p<0.01) and overweight (p<0.01) than the North +West zones. Excess weight and overweight prevalence in preschoolers in Natal is high, mainly in private schools, showing the need to implement prevention and intervention programs.


Preliminary study of Cytauxzoon felis infection in outdoor cats in Mashhad, Iran.
The objectives of the current study were to assess the preliminary status of Cytauxzoon felis (C. felis) infection among outdoor cats in Mashhad, Iran and also to compare clinicopathological findings between C. felis infected and non-infected cats. Blood samples were collected from 100 outdoor domestic cats between April and September in 2019. Infection with C. felis was determined using microscopic observation of giemsa-stained blood smears and molecular analysis. The piroplasms was microscopically detected in 5 (5%) of the blood smears with low parasitemia. The presence of C. felis was confirmed in one positive microscopy sample by PCR. The molecular assay revealed that 19 cats (19%) were infected with C. felis. Hematological and some serum biochemical factors were evaluated in both of the infected and non-infected cats. There was no association between C. felis infection and age, gender, and laboratory findings except for hematocrit (Hct) and concentration of total protein and globulin. Clinical signs such as fever, dehydration, lethargy, and icterus were observed only in 15.78% (3/19) of the infected cats, while 84.22% (16/19) were asymptomatic. Laboratory findings such as non-regenerative anemia, thrombocytopenia, neutrophilic leukocytosis hyperproteinemia, hypoalbuminemia, and hyperbilirubinemia were detected in the clinically infected cats. This study revealed the relatively high frequency of C. felis infection in outdoor domestic cats in Mashahd, Iran. The predominance of asymptomatic infection likely indicates that these cats may be infected with low-virulent strains of C. felis.


A Survey of the Impact of Deyolking on Biological Processes Covered by Shotgun Proteomic Analyses of Zebrafish Embryos.
Deyolking, the removal of the most abundant protein from the zebrafish (Danio rerio) embryo, is a common technique for in-depth exploration of proteome-level changes in vivo due to various environmental stressors or pharmacological impacts during embryonic stage of development. However, the effect of this procedure on the remaining proteome has not been fully studied. Here, we report a label-free shotgun proteomics survey on proteome coverage and biological processes that are enriched and depleted as a result of deyolking. Enriched proteins are involved in cellular energetics and development pathways, specifically implicating enrichment related to mitochondrial function. Although few proteins were removed completely by deyolking, depleted molecular pathways were associated with calcium signaling and signaling events implicating immune system response.


Efficient parameter estimation for spatio-temporal models of pattern formation: case study of Drosophila melanogaster.
Diffusable and non-diffusable gene products play a major role in body plan formation. A quantitative understanding of the spatio-temporal patterns formed in body plan formation, by using simulation models is an important addition to experimental observation. The inverse modelling approach consists of describing the body plan formation by a rule-based model, and fitting the model parameters to real observed data. In body plan formation, the data are usually obtained from fluorescent immunohistochemistry or in situ hybridizations. Inferring model parameters by comparing such data to those from simulation is a major computational bottleneck. An important aspect in this process is the choice of method used for parameter estimation. When no information on parameters is available, parameter estimation is mostly done by means of heuristic algorithms. We show that parameter estimation for pattern formation models can be efficiently performed using an evolution strategy (ES). As a case study we use a quantitative spatio-temporal model of the regulatory network for early development in Drosophila melanogaster. In order to estimate the parameters, the simulated results are compared to a time series of gene products involved in the network obtained with immunohistochemistry. We demonstrate that a (mu,lambda)-ES can be used to find good quality solutions in the parameter estimation. We also show that an ES with multiple populations is 5-140 times as fast as parallel simulated annealing for this case study, and that combining ES with a local search results in an efficient parameter estimation method.


Limited value of shape, margin and CT density in the discrimination between benign and malignant screen detected solid pulmonary nodules of the NELSON trial.
To evaluate prospectively the value of size, shape, margin and density in discriminating between benign and malignant CT screen detected solid non-calcified pulmonary nodules. This study was institutional review board approved. For this study 405 participants of the NELSON lung cancer screening trial with 469 indeterminate or potentially malignant solid pulmonary nodules (>50mm3) were selected. The nodules were classified based on size, shape (round, polygonal, irregular) and margin (smooth, lobulated, spiculated). Mean nodule density and nodule volume were automatically generated by software. Analyses were performed by univariate and multivariate logistic regression. Results were presented as likelihood ratios (LR) with 95% confidence intervals (CI). Receiver operating characteristic analysis was performed for mean density as predictor for lung cancer. Of the 469 nodules, 387 (83%) were between 50 and 500mm3, 82 (17%) >500mm3, 59 (13%) malignant, 410 (87%) benign. The median size of the nodules was 103mm3 (range 50-5486mm3). In multivariate analysis lobulated nodules had LR of 11 compared to smooth; spiculated nodules a LR of 7 compared to smooth; irregular nodules a LR of 6 compared to round and polygonal; volume a LR of 3. The mean nodule CT density did not predict the presence of lung cancer (AUC 0.37, 95% CI 0.32-0.43). In solid non-calcified nodules larger than 50mm3, size and to a lesser extent a lobulated or spiculated margin and irregular shape increased the likelihood that a nodule was malignant. Nodule density had no discriminative power.


Motility of the gastrointestinal tract and gallbladder during long-term total parenteral nutrition in dogs.
The motility of the gastrointestinal tract during total parenteral nutrition (TPN) remains poorly understood. The objective of this study was to determine the motility pattern not only in the gastrointestinal tract but also in the gallbladders of dogs maintained by TPN. Central venous catheters were inserted through the external jugular vein of 5 dogs and 6 strain gauge force transducers were sewn to the stomach, small intestine, and gallbladder. Two weeks later, oral food was discontinued and motility was recorded for 24 hours after the first migrating motor complex (MMC) was confirmed in the stomach as pre-TPN. TPN was started and continued for 4 weeks, and patterns of motor activity during TPN were recorded for 24 hours at the end of each week. The durations of MMC in the stomach, duodenum, and gallbladder in pre-TPN were 118 +/- 3 minutes, 118 +/- 2 minutes, and 118 +/- 2 minutes, respectively, but in the first week of TPN they were 432 +/- 56 minutes, 431 +/- 56 minutes, and 386 +/- 29 minutes, respectively. TPN times were significantly longer than those of pre-TPN (corrected p < .005). The durations of MMC in jejunoileum did not alter between pre-TPN and TPN. The occurrences of phase III in the stomach, duodenum, and gallbladder in pre-TPN were 12/d, but during TPN they were reduced significantly (corrected p < .005). TPN did not affect the motility of the jejunoileum but did inhibit the motor activities of the stomach, duodenum, and gallbladder. The inhibition of gallbladder contraction observed during TPN may be one of the factors inducing gallbladder disease.


Acoustic patterns of infant vocalizations expressing emotions and communicative functions.
The present study aimed at identifying the acoustic pattern of vocalizations, produced by 7- to 11-month-old infants, that were interpreted by their mothers as expressing emotions or communicative functions. Participants were 6 healthy, first-born English infants, 3 boys and 3 girls, and their mothers. The acoustic analysis of the vocalizations was performed using a pattern recognition (PR) software system. A PR system not only calculates signal features, it also automatically detects patterns in the arrangement of such features. The following results were obtained: (a) the PR system distinguished vocalizations interpreted as emotions from vocalizations interpreted as communicative functions with an overall accuracy of 87.34%; (b) the classification accuracy of the PR system for vocalizations that convey emotions was 85.4% and for vocalizations that convey communicative functions was 89.5%; and (c) compared to vocalizations that express emotions, vocalizations that express communicative functions were shorter, displayed lower fundamental frequency values, and had greater overall intensity. These findings suggest that in the second half of the first year, infants possess a vocal repertoire that contributes to regulating cooperative interaction with their mothers, which is considered one of the major prerequisites for language acquisition.


Thermal transport and phonon localization in periodich-GaN/h-AlN superlattices.
The widely observed non-diffusive phonon thermal transport phenomenon in nanostructures is largely attributed to classical size effects, which ignore the characteristic of phonon wave. In this context, the crossover transition process from incoherent to coherent phonon transport in two-dimensional heterogeneous periodich-GaN/h-AlN superlattices is demonstrated using a non-equilibrium molecular dynamics approach, where the localization behavior of thermal phonons is particularly significant. The results show that the thermal transport of the superlattice structure is affected by a combination of structural parameters and temperature. The thermal conductivity (TC) of the superlattice decreases and then increases as the interface density increases. Phonon-interface scattering dominates the incoherent phonon transport, while local phonons modulate the transport in the coherent region. Thus, the competition between phonon wave and particle properties causes the transition from incoherent to coherent phonon transport. In addition, as the TC valley depth slows down with increasing system temperature, the scattering of medium and high frequency phonons is enhanced and the phonon lifetime decreases. Research on localized phonons in superlattices provides theoretical support for thermal transport regulation in basal low-dimensional materials.


Cytochrome c folding kinetics studied by time-resolved electrospray ionization mass spectrometry.
A new method for studying the folding kinetics of proteins is described. The method combines a continuous flow mixing technique with an electrospray mass spectrometer. Different protein conformations in solution are detected by the different charge states they produce during electrospray ionization. Unfolded proteins generally have more accessible protonation sites and give higher charge states than native proteins. The method is applied to study the refolding of acid-denatured cytochrome c. Global data analysis is used to obtain the exponential lifetimes which are associated with the refolding process. The kinetics can be described by two lifetimes of 0.17 +/- 0.02 and 8.1 +/- 0.9 s which are in accordance with the results of stopped flow experiments previously described in the literature. These lifetimes are associated with roughly 90 and 10% of the total intensity changes in the mass spectrum, respectively, and most likely reflect fast and slow refolding subpopulations of cytochrome c in solution.


[Study on the sweat regulation mechanism under different temperature circumstance and different intensive exercise].
To investigate the sweat regulation mechanism of human body. Arm muscular work was performed on bicycle ergometer by eight healthy male subjects on 20 W and 40 W work loads lasting 10 min or 20 min in 16 degrees C and 21 degrees C ambient temperature. Sweat, metabolic rate and corresponding skin and core temperature changes were measured during different periods. Sweat varied directly with ambient temperature and there were the corresponding changes in mean skin temperature, rectal temperature and metabolic rate. And when the work load was elevated, the skin temperature at chest and metabolic rate increased as sweat increased. There were no differences in the physiological indices between 20 W 20 min and 20 W 10 min, but mean skin temperature and sweat rate during 40 W 20 min work were higher than 40 W 10 min while metabolic rate did not change. The time when chest temperature arrived at the threshold was in correspondence with obvious sweat onset. Both local skin temperature at chest and metabolic rate were significantly correlated with sweat, but the latter was stronger. The regression equation relating metabolic rate and sweat rate was compound function. Skin temperature was important for sweat onset, and the sweat predicted model based on the metabolic rate or ambient temperature was more suitable and practical.


Long-term Outcomes of Partial Trapeziectomy With Capsular Interposition Arthroplasty for Osteoarthritis of the Thumb Basal Joint.
The purpose of this study was to describe long-term outcomes of partial trapeziectomy with capsular interposition (PTCI) arthroplasty for patients with osteoarthritis of the basal joint of the thumb. A total of 27 patients (20 women, 7 men; 32 thumbs) with a mean age of 61 years (range, 47-74 years) agreed to return for follow-up and were included in the study. Mean postoperative follow-up was 64.3 months (range, 28-112 months). Evaluation included tests for grip and pinch strength; range of motion of the metacarpophalangeal joint; measurement of the first web space; completion of the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire; visual analog scale (VAS) measurements; and radiographic examination of the hand. A paired, 2-tailed t test was used to determine statistical significance (P<.05) of pre- and postoperative values. Postoperative values for grip strength were significantly increased from preoperative values. No significant loss of pinch strength was noted. Excessive hyperextension of the metacarpophalangeal joint did not occur, and the first web space was maintained. The mean DASH questionnaire and VAS scores were 5.06 (range, 0-26.5) and 0.32, respectively. Use of PTCI arthroplasty resulted in minimal loss in thumb height (7%) and significantly reduced thumb metacarpal subluxation (13%). There were no reported complications. The low DASH questionnaire and VAS scores compare well with other studies and indicate good functional outcomes. In treating thumb basal joint osteoarthritis, use of PTCI arthroplasty may result in improved thumb stability and grip strength, minimal subsidence of the thumb metacarpal, and reduced joint subluxation. [Orthopedics. 2018; 41(2):e228-e233.].


The wavelet transform as a tool for recognition of biosignals.
The use of the wavelet transform as a signal analysis tool has been demonstrated by its successful application to the study of various signals. The first step in addressing pattern recognition problems is to define a representation that can be used for extracting the information content of signals. The sharp variation points of a signal amplitude are among the meaningful characterizations of the signal. The wavelet transform of the signal is found to be translation variant which makes it difficult for direct application in pattern recognition. However, the zero-crossings of a wavelet transform employing a particular class of wavelets can provide the translation invariant locations of the signal variation points. A zero-crossing representation augmented by the measure of the structure between the two consecutive zero-crossings has been studied by Stephane Mallat. On the basis of this representation, we demonstrate recognition of segments of biosignals embedded in streams of signals. The feasibility of employing zero-crossings of a wavelet transform as a tool in searching for a particular pattern class in the library of biosignals is explored.


Signal-to-Noise Ratio in PVT Performance as a Cognitive Measure of the Effect of Sleep Deprivation on the Fidelity of Information Processing.
There is a long-standing debate about the best way to characterize performance deficits on the psychomotor vigilance test (PVT), a widely used assay of cognitive impairment in human sleep deprivation studies. Here, we address this issue through the theoretical framework of the diffusion model and propose to express PVT performance in terms of signal-to-noise ratio (SNR). From the equations of the diffusion model for one-choice, reaction-time tasks, we derived an expression for a novel SNR metric for PVT performance. We also showed that LSNR-a commonly used log-transformation of SNR-can be reasonably well approximated by a linear function of the mean response speed, LSNRapx. We computed SNR, LSNR, LSNRapx, and number of lapses for 1284 PVT sessions collected from 99 healthy young adults who participated in laboratory studies with 38 hr of total sleep deprivation. All four PVT metrics captured the effects of time awake and time of day on cognitive performance during sleep deprivation. The LSNR had the best psychometric properties, including high sensitivity, high stability, high degree of normality, absence of floor and ceiling effects, and no bias in the meaning of change scores related to absolute baseline performance. The theoretical motivation of SNR and LSNR permits quantitative interpretation of PVT performance as an assay of the fidelity of information processing in cognition. Furthermore, with a conceptual and statistical meaning grounded in information theory and generalizable across scientific fields, LSNR in particular is a useful tool for systems-integrated fatigue risk management.


[Pyridoxine for severe metabolic acidosis and seizures due to isoniazid overdose].
A 15-year-old girl took 3 g of isoniazid (15 tablets) in a suicide attempt and was brought unconscious to the emergency room. She was in respiratory failure, with seizures that could not be stopped with diazepam. Severe metabolic acidosis with normal serum lactate developed (pH 6.85), but did not improve after infusion of bicarbonate. Intravenous administration of pyridoxine led to prompt cessation of the seizures and to gradual improvement of acid-base status. She recovered consciousness after several hours and was discharged a week later.


Nurses' views about returning to practice after a career break.
Shortages in nursing staff have led to recruitment campaigns targeting nurses who have left the profession. The present study explored reasons why career-break nurses decide for or against a return to practice, as well as perceptions of nursing following return. Semistructured interview were conducted with 24 nurses who had returned recently to the profession and 28 nurses on a "career break". Findings revealed that those who returned did so when their personal circumstances allowed, and half returned as bank nurses in order to work flexible, family-friendly hours. Some non-returners reported that they could not afford to return because of childcare costs. Although still a caring one, the nurse's role is seen by returners as becoming increasingly technologically and administratively demanding. Flexibility with regard to working practices, increased salaries and demonstrating that it values its staff, were highlighted by interviewees generally as priority issues for the NHS if it wishes to recruit career-break nurses.


Blocking cardiac growth in hypertrophic cardiomyopathy induces cardiac dysfunction and decreased survival only in males.
Mutations in myosin heavy chain (MyHC) can cause hypertrophic cardiomyopathy (HCM) that is characterized by hypertrophy, histopathology, contractile dysfunction, and sudden death. The signaling pathways involved in the pathology of HCM have not been elucidated, and an unresolved question is whether blocking hypertrophic growth in HCM may be maladaptive or beneficial. To address these questions, a mouse model of HCM was crossed with an antihypertrophic mouse model of constitutive activated glycogen synthase kinase-3beta (caGSK-3beta). Active GSK-3beta blocked cardiac hypertrophy in both male and female HCM mice. However, doubly transgenic males (HCM/GSK-3beta) demonstrated depressed contractile function, reduced sarcoplasmic (endo) reticulum Ca(2+)-ATPase (SERCA) expression, elevated atrial natriuretic factor (ANF) expression, and premature death. In contrast, female HCM/GSK-3beta double transgenic mice exhibited similar cardiac histology, function, and survival to their female HCM littermates. Remarkably, dietary modification from a soy-based diet to a casein-based diet significantly improved survival in HCM/GSK-3beta males. These findings indicate that activation of GSK-3beta is sufficient to limit cardiac growth in this HCM model and the consequence of caGSK-3beta was sexually dimorphic. Furthermore, these results show that blocking hypertrophy by active GSK-3beta in this HCM model is not therapeutic.


[Follow-up assessment of intratympanic gentamicin therapy and Saccotomia in Menière's Disease].
The intratympanic application of ototoxic antibiotics and saccotomia have been well documented in severe cases of one-sided Menière's disease for 30 years now. Both treatment methods are still subject to controversial discussion. This study includes 8 patients suffering from persistent one-sided Menière's disease after treatment with gentamicin application and additional saccotomia (n=2). We performed follow-up visits including the assessment of hearing ability, vestibular function and cranial MRI, 2-10 years after onset of treatment. After therapeutic interventions 7 patients reported to be healed of their symptom vertigo. In 4 patients the gentamicin-treated vestibular organ did not respond to thermic stimulus at the time of follow-up examination. Auditory threshold shift was observed in 3 patients (1 permanent, 2 temporary), whereas hearing threshold improved in 2 patients. Tinnitus was attenuated in 3 patients, while 1 patient suffered from posttherapeutic onset of tinnitus. Morphological and structural changes due to Menière's disease and treatment procedures were ruled out by cranial MRI. The intratympanic application of ototoxic medication is a safe and effective treatment method in severe cases of Menière's disease. Saccotomia should be considered as therapeutic regimen for persistent symptoms after repeated application of gentamicin.


Cultivation of Aquincola tertiaricarbonis L108 on the fuel oxygenate intermediate tert-butyl alcohol induces aerobic anoxygenic photosynthesis at extremely low feeding rates.
Aerobic anoxygenic photosynthesis (AAP) is found in an increasing number of proteobacterial strains thriving in ecosystems ranging from extremely oligotrophic to eutrophic. Here, we have investigated whether the fuel oxygenate-degrading betaproteobacterium Aquincola tertiaricarbonis L108 can use AAP to compensate kinetic limitations at low heterotrophic substrate fluxes. In a fermenter experiment with complete biomass retention and also during chemostat cultivation, strain L108 was challenged with extremely low substrate feeding rates of tert-butyl alcohol (TBA), an intermediate of methyl tert-butyl ether (MTBE). Interestingly, formation of photosynthetic pigments, identified as bacteriochlorophyll a and spirilloxanthin, was only induced in growing cells at TBA feeding rates less than or equal to maintenance requirements observed under energy excess conditions. Growth continued at rates between 0.001 and 0.002 h(-1) even when the TBA feed was decreased to values close to 30 % of this maintenance rate. Partial sequencing of genomic DNA of strain L108 revealed a bacteriochlorophyll synthesis gene cluster (bchFNBHL) and photosynthesis regulator genes (ppsR and ppaA) typically found in AAP and other photosynthetic proteobacteria. The usage of light as auxiliary energy source enabling evolution of efficient degradation pathways for kinetically limited heterotrophic substrates and for lowering the threshold substrate concentration Smin at which growth becomes zero is discussed.


BF2.649 [1-{3-[3-(4-Chlorophenyl)propoxy]propyl}piperidine, hydrochloride], a nonimidazole inverse agonist/antagonist at the human histamine H3 receptor: Preclinical pharmacology.
Histamine H3 receptor inverse agonists are known to enhance the activity of histaminergic neurons in brain and thereby promote vigilance and cognition. 1-{3-[3-(4-Chlorophenyl)propoxy]propyl}piperidine, hydrochloride (BF2.649) is a novel, potent, and selective nonimidazole inverse agonist at the recombinant human H3 receptor. On the stimulation of guanosine 5'-O-(3-[35S]thio)triphosphate binding to this receptor, BF2.649 behaved as a competitive antagonist with a Ki value of 0.16 nM and as an inverse agonist with an EC50 value of 1.5 nM and an intrinsic activity approximately 50% higher than that of ciproxifan. Its in vitro potency was approximately 6 times lower at the rodent receptor. In mice, the oral bioavailability coefficient, i.e., the ratio of plasma areas under the curve after oral and i.v. administrations, respectively, was 84%. BF2.649 dose dependently enhanced tele-methylhistamine levels in mouse brain, an index of histaminergic neuron activity, with an ED50 value of 1.6 mg/kg p.o., a response that persisted after repeated administrations for 17 days. In rats, the drug enhanced dopamine and acetylcholine levels in microdialysates of the prefrontal cortex. In cats, it markedly enhanced wakefulness at the expense of sleep states and also enhanced fast cortical rhythms of the electroencephalogram, known to be associated with improved vigilance. On the two-trial object recognition test in mice, a promnesiant effect was shown regarding either scopolamine-induced or natural forgetting. These preclinical data suggest that BF2.649 is a valuable drug candidate to be developed in wakefulness or memory deficits and other cognitive disorders.


[Comparative study on dose-toxicity-effect of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets on CIA model rats].
The aim of this paper was to compare the properties of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets from dose-effect-toxicity on type Ⅱ collagen-induced arthritis( CIA) in rats. SD rats were randomly divided into eight groups,including normal group,model group,Tripterygium Glycosides Tablets groups( 1 times equivalent dose 0.009 g·kg-1,4 times equivalent dose 0.036 g·kg-1,16 times equivalent dose 0.144 g·kg-1),Tripterygium wilfordii Tablets groups( 1 times equivalent dose 0.007 5 mg·kg-1,4 times equivalent dose 0.030 mg·kg-1,16 times equivalent dose 0.120 mg·kg-1). Beginning on the first immunization,Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets administered intraperitoneally once a day. After the second immunization,the symptoms such as redness and swelling of joints were observed,and the clinical score and incidence of arthritis were evaluated. HE and Masson staining were used to examine the histopathological changes of joints. The expression level of anti-type Ⅱ collagen antibody Ig G in serum was detected by ELISA,routine testing of blood components,the concentration of ALP( alkaline phosphatase),ALT( alanine aminotransferase),AST( aspartate aminotransferase),GGT( gamma-glutamyltransferase),TBi L( total bilirubin),CRE( creatinine) and UREA( urea) in serum were detected by enzymatic assay. The rate of sperm deformity in the epididymis was evaluated under light microscope. The extent of damage to the testis and ovarian tissue was assessed by HE staining. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets attenuated the inflammation,redness,swelling and deformity of joints and reduced the clinical score and incidence of arthritis in CIA rats. Meanwhile,it also exhibited obvious reduction in all pathological features such as joint synovitis,pannus,cartilage erosion and bone destruction. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets reduced Ig G in a dose-dependent manner,and Tripterygium Glycosides Tablets is better than Tripterygium wilfordii Tablets( P<0.05 or P<0.01). The high doses of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets could significantly increase the organ coefficient of liver and spleen and reduced RBC and HGB in CIA rats( P<0.01),and severity leading to death. Gastric mucosal injury and morphological changes of liver and kidney were not observed in CIA rats of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets treatment group. The 4 and 16 times doses of Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets could significantly increase serum ALT,GGT and decrease CRE( P<0.05 or P<0.01). Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets could increase the sperm deformity rate and damage the testicular seminiferous tubules of CIA male rats. Severity increased with dose and time increasing. The effect of Tripterygium Glycosides Tablets( 16 times) is more significant than Tripterygium wilfordii Tablets( 16 times). Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets significantly delayed onset of arthritis and inhibited the paw edema and arthritic score. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets also caused male reproductive damage,high dose affected hematopoiesis,and maximum dose leading to death. Tripterygium Glycosides Tablets and Tripterygium wilfordii Tablets all depended on dose-effect-toxicity manner. Anti-arthritis effect of Tripterygium Glycosides Tablets is better than Tripterygium wilfordii Tablets,but the toxicity of Tripterygium Glycosides Tablets maximum dose is more obvious. The relevant conclusions of our study will provide experimental references for clinical rational use of drugs,and further clinical studies are needed to confirm our conclusions.


Young Person and Parent Perspectives on the Impact of Cleft Lip and/or Palate Within an Educational Setting.
During the school years, a cleft of the lip and/or palate (CL/P) may pose a risk to educational achievement. To further understand this multifaceted association, and to offer suggestions as to how young people's educational experiences might be improved, qualitative investigation is warranted. Semi-structured telephone interviews were conducted with young people born with CL/P (n = 10; aged 10-16 years) and their parents (n = 10). The resulting data were subjected to inductive thematic analysis. Negative social interactions, cleft-related treatment, the presence of an additional condition, and a lack of appropriate support from teachers was found to influence young people's educational experience. Methods for promoting diversity, support from clinical teams, facilitation of positive school transitions, implementation of training for teachers, and a holistic approach to the measurement of "success" were suggested by participants as potential ways of improving this experience. The findings of this study point to a need for a range of school-focused interventions, as well as the inclusion of a number of potentially impactful variables within future quantitative research.


On the regularization of impact without collision: the Painlevé paradox and compliance.
We consider the problem of a rigid body, subject to a unilateral constraint, in the presence of Coulomb friction. We regularize the problem by assuming compliance (with both stiffness and damping) at the point of contact, for a general class of normal reaction forces. Using a rigorous mathematical approach, we recover impact without collision (IWC) in both the inconsistent and the indeterminate Painlevé paradoxes, in the latter case giving an exact formula for conditions that separate IWC and lift-off. We solve the problem for arbitrary values of the compliance damping and give explicit asymptotic expressions in the limiting cases of small and large damping, all for a large class of rigid bodies.


[Influence of complications on independence of patients with spinal cord injury in early rehabilitation].
To evaluate the influence of complications on independence of patients after spinal cord injury during rehabilitation. Data were collected on 130 patients with spinal cord injury admitted to the Clinic of Rehabilitation, Kaunas University of Medicine Hospital in 1999-2004. The study population consisted of 94 (72.3%) males and 36 (27.7%) females. Their age ranged from 16 to 80 years. The functional improvement was determined in terms of progress in independence in twelve daily living skills using Functional Independence Measure scale. Neurological status was evaluated by Standard Neurological Classification of traumatic spinal cord injury. Also, during early rehabilitation period complications were evaluated. Patients were divided into two groups: patients with complications and patients without complications during rehabilitation. More passive occupational therapy procedures were applied to patients with complications in comparison with patients without complications. The results of the study showed that 44 (33.8%) cases were without complications during rehabilitation and 86 (66.2%) patients had complications. The most frequent complications were chronic pain (55.8%), urinary infection (43%), spasticity (30.2%) and pressure ulcers (20.9%). No statistically significant dependence was found between the rate of complications and age, gender and level of injury (p>0.05). Statistically significant dependence has been observed only between the rate of complication and completeness of injury (p<0.05). The change of the increased independence of patients without complications during rehabilitation was statistically significantly greater in comparison with patients who had complications (p<0.05).