Estimating global marine surface microplastic abundance: systematic literature review.
Toxicity and persistence of microplastics (MP) in the marine environment has a potential to disturb the ecological balance of the planet. To evaluate the gravity of the situation, continuity in research of MP abundance is required. In this work for the first time a systematic literature review was conducted to build abundance datasets of MP at marine surface waters that were used to estimate average MP abundance and produce maps. Due to non-Gaussian distribution of the data, non-parametric statistics were used. The results show that an estimated average of approximately 6300 MP km-2 MP float at the surface of the oceans. Additionally, observations of drawbacks in MP research that hamper inter-research comparability were made and these mainly include heterogeneity of methods and poor reporting practice. Basic guidelines to improve future research comparability were devised. Results provided here can be beneficial to research that requires a reliable and comparable MP abundance datasets sourced in a transparent and rigorous manner. These datasets are made available to the readers.


The clinical course of patients with septic abortion admitted to an intensive care unit.
The purpose of this study was to describe the clinical course, complications, and outcome of patients with septic abortion admitted to the intensive care unit (ICU). In this retrospective study, the records of 63 patients with septic abortion admitted to the ICU of a university hospital in Argentina between 1985 and 1995 were reviewed. The mean age of the patients was 28.5 years, and 33% had had previous abortions. The mean gestational age was 10.5 weeks. The first ICU day Acute Physiology and Chronic Health Evaluation (APACHE) II mean score was 13.9. Acute renal failure developed in 73% (46 of 63) of the patients, disseminated intravascular coagulation (DIC) in 31% (15 of 49), and septic shock in 32% (20 of 63). Blood cultures were positive in 24% (15 of 62). Twelve patients died (19%). Eight of the deaths occurred during the first 48 h of the ICU admission. Compared with survivors, non-survivors had higher median number of organ failures (1.0 vs 4.0, p<0.0001), mean first ICU day SOFA scores (6.6 vs 10.0, p=0.0059), and mean APACHE II scores (12.7 vs 20.2, p=0.0003), and were more likely to have septic shock (18 vs 92%, p<0.0001), and receive dopamine (37 vs 83%, p=0.0040), mechanical ventilation (8 vs 83%, p<0.0001), and pulmonary artery catheter (8 vs 41%, p=0.0026). Although it is an avoidable complication, septic abortion requiring admission to the ICU is associated with high morbidity and mortality.


Randomized controlled trial of pegbovigrastim as an adjunct therapy for naturally occurring severe clinical mastitis cases in dairy cows.
The main objective of this study was to quantify the effect of pegbovigrastim (PEG) as an adjunct therapy for naturally occurring severe mastitis cases on survival, intramammary bacteriological cure, and subsequent milk production. A double-blinded, randomized controlled trial was conducted on a single commercial dairy farm. During the study period, all cows having a case of severe clinical mastitis, defined as the presence of abnormal milk and inflammation in one quarter or more combined with the presence of systemic signs (pyrexia, dehydration, or recumbency), were enrolled in the study. In addition to a standardized therapy combining systemic and intramammary antimicrobials as well as systemic anti-inflammatory drugs, cows received a subcutaneous injection of either 2.7 mL of 0.9% sterile saline (control group; CON) or 2.7 mL of PEG (PEG group). A milk sample for bacteriological analysis was taken before treatment was administered and a second sample was taken 14 d after enrollment. Survival (30 d post-treatment) and bacteriological cure (14 d post-treatment) were analyzed by survival analysis and chi-squared tests, respectively, whereas daily milk production was treated as a repeated measure in mixed regression models. The 77 cows enrolled in the study were of parity 2 to 4 (mean = 3) and between 3 and 302 d in milk (mean = 154). The bacteria identified in milk at enrollment were Klebsiella spp. (n = 48; 62%), Escherichia coli (n = 16; 21%), Enterobacter spp. (n = 10; 13%), or no growth (n = 3; 4%). The probability of survival during the first 30 d after treatment was higher in the PEG group (84%) than in the control group (46%). Daily milk production over the 30-d period following treatment and bacteriological cure 14 d post-treatment did not differ between groups. Overall, cows treated with PEG as an adjunct therapy for naturally occurring cases of severe clinical mastitis had a better survival than cows treated with saline.


Transcriptional regulation of CYP19A1 expression in chickens: ESR1, ESR2 and NR5A2 form a functional network.
Aromatase, encoded by CYP19A1, is responsible for the conversion of androgen to estrogen, which plays a vital role in the development and function of the ovary and functions in many other physiological processes in both sexes. Instead of being expressed in ovarian granulosa cells, as in mammals, CYP19A1 is expressed in chickens in the theca cells of ovarian follicles, and the mechanism of CYP19A1 expression regulation remains unknown. Here, using immunofluorescence and western blotting assay, we first confirmed that CYP19A1 and FOXL2 (Forkheadbox L2) were coexpressed in pre-granulosa cells of female chicken embryonic gonads, while FOXL2 did not affect aromatase expression at embryonic stages. Second, our research showed that CYP19A1, ESR1 (estrogen receptor alpha), ESR2 (estrogen receptor beta) and NR5A2 (liver receptor homologue-1) were coexpressed in the theca cell layers of chicken small yellow follicles. There was cross-talk between CYP19A1 and candidate transcription factors (ESR1, ESR2 and NR5A2), which was identified by generating a reliable theca cell culture model. Using luciferase assays in theca cells and chicken embryonic fibroblast (DF-1) cells, the results suggested that ESR1 and NR5A2 had potential effects on CYP19A1 promoter activity in chickens. Overexpression of ESR1, ESR2 and NR5A2 in chicken embryonic fibroblast (DF-1) cells upregulated the protein expression of CYP19A1, mutually restricted each other and formed a potential regulatory network to coordinate the expression of CYP19A1. To conclude, our results indicated that FOXL2 cannot regulate the expression of CYP19A1 at chicken embryonic stages and after sexual maturity, ESR1, ESR2 and NR5A2 form a functional network to affect the expression of CYP19A1. These results laid a foundation for further research on the transcriptional regulation of chicken aromatase.


Crohn's colitis: the fate of the rectum.
Previous reports suggest that up to 70% of patients undergoing surgery for Crohn's disease of the large bowel do not have gastrointestinal continuity restored and require a permanent ileostomy. In this study the experience with patients requiring surgical treatment of large bowel Crohn's disease is reviewed with particular reference to the management of the rectum. The records of 19 elective and 25 urgent colonic resections performed for large bowel Crohn's disease in 44 patients (16 males, 28 females; mean age 41 years, range 17-76) between 1983 and 1995 were reviewed. Staged proctectomy was performed in 5 of 12 patients who had colectomy for acute colitis and in one patient who had had an elective colectomy. Permanent ileostomy was required in 72% of patients with acute Crohn's colitis and 84% of patients who had elective surgery for large bowel Crohn's. Over 70% of patients having surgical treatment of Crohn's disease of the large bowel required permanent ileostomy. No cases of cancer developed in patients with retained rectal stumps.


Requirement of sperm-oocyte plasma membrane fusion for establishment of the plasma membrane block to polyspermy in human pronuclear oocytes.
We investigated whether the incorporation of the sperm membrane into the oolemma contributes to the human plasma membrane block to polyspermy. We used zona pellucida-free oocytes fertilized by intracytoplasmic sperm injection (ICSI) or activated by parthenogenetic activation. Only two of the 35 pronuclear oocytes fertilized by spermatozoa (control) demonstrated one single penetrating spermatozoa. In contrast, the majority of ICSI and parthenogenetically activated pronuclear oocytes were penetrated with an average of three spermatozoa per oocyte. The number of fused and binding spermatozoa of ICSI and parthenogenetically activated oocytes were significantly higher than in control oocytes (3.5+/-0.6 and 4.3+/-0.6 for ICSI; 3.0+/-0.3 and 3.8+/-0.4 for activated and 0.2+/-0.1 and 0.6+/-0.2 for controls, respectively, P < 0.01). Furthermore, the cortical granules were released from the cortex of ICSI and calcium ionophore-puromycin-activated pronuclear oocytes to the same extent as that of pronuclear oocytes fertilized by spermatozoa. These results suggest that the establishment of the plasma membrane block to sperm penetration in the human oocyte may require a fusion process between sperm and oocyte plasma membranes.


Effects of a guanine-derived formamidopyrimidine lesion on DNA replication: translesion DNA synthesis, nucleotide insertion, and extension kinetics.
2,6-Diamino-4-hydroxy-5-formamidopyrimidine derived from guanine (FapyG) is a major DNA lesion formed by reactive oxygen species. In this study, a defined oligonucleotide template containing a 5-N-methylated analog of FapyG (mFapyG) was prepared, and its effect on DNA replication was quantitatively assessed in vitro. The results were further compared with those obtained for 7,8-dihydro-8-oxoguanine and an apurinic/apyrimidinic site embedded in the same sequence context. mFapyG constituted a fairly strong but not absolute block to DNA synthesis catalyzed by Escherichia coli DNA polymerase I Klenow fragment with and without an associated 3'-5' exonuclease activity, thereby permitting translesion synthesis with a limited efficiency. The efficiency of translesion synthesis was G > 7,8-dihydro-8-oxoguanine > mFapyG > apurinic/apyrimidinic site. Analysis of the nucleotide insertion (f(ins) = V(max)/K(m) for insertion) and extension (f(ext) = V(max)/K(m) for extension) efficiencies for mFapyG revealed that the extension step constituted a major kinetic barrier to DNA synthesis. When mFapyG was bypassed, dCMP, a cognate nucleotide, was preferentially inserted opposite the lesion (dCMP (relative f(ins) = 1) dTMP (2.4 x 10(-4)) approximately dAMP (8.1 x 10(-5)) > dGMP (4.5 x 10(-7))), and the primer terminus containing a mFapyG:C pair was most efficiently extended (mFapyG:C (relative f(ext) = 1) > mFapyG:T (4.6 x 10(-3)) mFapyG:A and mFapyG:G (extension not observed)). Thus, mFapyG is a potentially lethal but not premutagenic lesion.


West Nile virus infection of adult mice by oral route.
Adult Swiss albino mice were fed orally with suspensions of a strain of West Nile virus isolated in Nigeria. Most of these mice became sick and died 7 days post feeding and virus was recovered from organs of such infected mice. Histological lesions were observed in some tissues and antibody to the strain of West Nile virus developed in mice that survived infection.


Salmonella mutagenicity tests: IV. Results from the testing of 300 chemicals.
Three hundred chemicals were tested for mutagenicity, under code, in Salmonella typhimurium, using a preincubation protocol. All tests were performed in the absence of exogenous metabolic activation, and in the presence of liver S-9 from Aroclor-induced male Sprague-Dawley rats and Syrian hamsters. The results and data from these tests are presented.


Social-cognitive predictors of dietary behaviors in South Korean men and women.
Eating a diet that is high in vitamins and low in fat is considered to be governed by social-cognitive factors, such as intentions, planning, self-efficacy, and outcome expectancies. A longitudinal field study was designed to examine the interrelationships of these factors with dietary behaviors. In 697 South Korean men and women, objective health-risk status was assessed at Time 1 (cholesterol, blood pressure, and body mass index) in conjunction with self-efficacy, outcome expectancies, and intentions. At Time 2, six months later, coping self-efficacy, planning, and dietary behaviors were measured. A two-group structural equation model for men and women was specified to determine the relations of distal and proximal predictors of a healthy diet. Self-efficacy was of equal predictive power in men and women, whereas intentions and planning were relevant only in women. Objective risk status was associated with intentions in women but not in men. Results confirm the predictive power of the Health Action Process Approach and point to the role of gender in the self-regulation of dietary behaviors.


The principles of ultrasound and its application in freezing related processes of food materials: A review.
Ultrasonic processing is a novel and promising technology in food industry. The propagation of ultrasound in a medium generates various physical and chemical effects and these effects have been harnessed to improve the efficiency of various food processing operations. Ultrasound has also been used in food quality control as diagnostic technology. This article provides an overview of recent developments related to the application of ultrasound in low temperature and closely related processes such as freezing, thawing, freeze concentration and freeze drying. The applications of high intensity ultrasound to improve the efficiency of freezing process, to control the size and size distribution of ice crystals and to improve the quality of frozen foods have been discussed in considerable detail. The use of low intensity ultrasound in monitoring the ice content and to monitor the progress of freezing process has also been highlighted.


"Dideoxy" RNA sequencing: a rapid method for studying genetic information.
The chain termination sequencing technique on RNA is a very rapid, direct method for the analysis of genetic information. It is particularly suitable for analysing systems on which microgram amounts of 50% pure RNA can be made available and for which numerous data are needed in order to derive genetic or structural information. The usefulness and limitations of the technique are discussed.


Effect of alpha-tocopherol and dose sensitivity on pancreatitis formation in rats with experimental pancreatitis.
Acute pancreatitis is an inflammatory disease accompanied by pancreatic inflammation characterized by acinar cell damage and leukocyte infiltration in the tissue. At present, mortality and morbidity rates are high despite the current treatment of pancreatitis; therefore, new studies and treatment studies are needed. In this study, the effects of alpha-tocopherol on different doses of L-arginine-induced experimental acute pancreatitis model were investigated. Thirty adult male Sprague-Dawley albino rats were randomly divided into four groups; control (sham) group (n=6), acute pancreatitis group (n=8), low-dose alpha-tocopherol (200 mg/kg once intraperitoneal [IP]) group (n=8), and high dose alpha-tocopherol (400 mg/kg once ip) group (n=8). Experimental acute pancreatitis model was created by a single IP dose of 5 g/kg of L-arginine. Alpha-tocopherol was administered in a single dose intraperitoneally, 30 min before the creation of the experimental model of acute pancreatitis induced by L-arginine induction in Groups 3 and 4. Tissue and blood samples were taken under anesthesia 72 h after L-arginine injection; then the rats were sacrificed by decapitation. Serum amylase, lipase, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-alpha, and C-reactive protein (CRP) levels were examined. Pancreatic tissue samples were examined under a light microscope for histopathological examination. When the acute pancreatitis group (Group 2) was compared to the control group (Group 1), serum amylase, lipase, IL-1β, IL-6, TNF-alpha, and CRP levels were all significantly increased (p<0.05 for all). Histopathological examination showed significant difference in edema (p<0.001) and inflammation (p=0.007) scores. When the low (Group 3) and high (Group 4) dose alpha-tocopherol groups were compared to Group 2, amylase, lipase, IL-1β, IL-6, TNF-alpha, and CRP parameters were statistically significantly lower (p<0.05 for all). In the histopathological comparison of Groups 2, 3, and 4, edema and inflammation scores were decreased in Groups 3 and 4 compared to Group 2. Comparing Group 4 to Group 3, lipase (p<0.01), IL-6 (p=0.038), and TNF-alpha (p=0.002) levels were significantly decreased; no significant difference was observed in the histopathological evaluation. Alpha-tocopherol was found to reduce inflammation and pancreatic damage in acute pancreatitis and was more effective in high doses.


Viscosity measurements of a ferrofluid: comparison with various hydrodynamic equations.
Effective viscosity of a magnetic fluid as a function of applied magnetic field oriented in the perpendicular direction of the capillary flow is determined. Close agreement with the Shliomis expression derived on the basis of effective field method is observed.


Tabanus arenivagus (diptera: tabanidae) attracted to ultraviolet light suction traps in Israel.
Suction blacklight trappings have been conducted at Bet Dagan since 1978. Tabanus arenivagus has been caught only during 1992-94. Seventy-one specimens, all females, were caught by these traps, demonstrating that females are attracted to the wavelength range of 340-380 nm radiated by the mercury-vapor lamps of these traps. This constitutes a new finding among the Tabanidae species of the Mediterranean region.


Excitatory and inhibitory A- and C-reflexes in pelvic parasympathetic efferent nerves elicited by single shock to A and C afferent fibers of perineal and limb somatic nerves in anesthetized rats.
The effects of single electrical shocks to myelinated A and unmyelinated C afferent fibers of perineal and limb somatic nerves on the reflex discharges in pelvic parasympathetic (L6/S1) efferent nerves to the bladder were examined in anesthetized central nervous system (CNS)-intact and acute spinal rats. When the bladder was empty, stimulation of perineal somatic inputs to the L6 and S1 segments from the perineo-femoral branch of a pudendal nerve produced excitatory A- and C-reflex discharge components in postganglionic parasympathetic efferent nerve branches on the bladder surface. When the bladder was expanded and pelvic efferent neurons were rhythmically active, additional inhibitory A- and C-reflex components could be seen. After acute spinal transection, the same stimuli elicited excitatory A- and C-reflex discharges of similar latency as those observed before the spinal transection, but were of larger amplitude and longer duration; resting activity in the pelvic nerve was low, and no evoked inhibitory reflex components could be observed. Electrical stimulation of afferents in the tibial nerve had no effect when the bladder pressure was low, but when the bladder was distended, early and late components of reflex inhibition and excitation of parasympathetic activity were visible in CNS-intact rats; these reflex responses were abolished following spinalization.


Lineage associated expression of virulence traits in bovine-adapted Staphylococcus aureus.
Bovine mastitis is the most costly disease to the dairy industry worldwide with Staphylococcus aureus commonly associated with intramammary infections that are persistent and refractory to treatment. The strains of S. aureus that cause mastitis predominantly belong to a number of well-described bovine-adapted lineages. The objective of this study was to determine if a variety of potential virulence traits were associated with lineage. Bovine-adapted S. aureus isolates (n=120), belonging to lineages CC97, CC151 and ST136, were tested for their ability to adhere to and internalise within cultured bovine mammary epithelial cells (bMEC), to bind bovine fibronectin, to form a biofilm in TSB, TSB+1% glucose and TSB+4% NaCl, and to induce an immune response from bMEC. There were no significant differences between the lineages in ability to adhere to or internalise within bMEC although there were significant differences between individual isolates. For lineages CC97 and ST136, mammalian cell adherence was correlated with the ability to bind bovine fibronectin, however isolates from CC151 could not bind bovine fibronectin in vitro, but adhered to bMEC in a fibronectin-independent manner. There were significant differences between the lineages in ability to form a biofilm in all three growth media with ST136 forming the strongest biofilm while CC151 formed the weakest biofilm. Lineages also differed in their ability to elicit an immune response from bMEC with CC97 eliciting a stronger immune response than CC151 and ST136. These data indicate the potential for both lineage and strain-specific virulence and a strain-specific response to infection in vivo and caution against extrapolating an effect from a single strain of S. aureus to draw conclusions regarding virulence or the host response to infection in unrelated lineages.


Reducing neuroinflammation via therapeutic compounds and lifestyle to prevent or delay progression of Parkinson's disease.
Parkinson's disease (PD) is the second most common age-associated neurodegenerative disorder and is characterised by progressive loss of dopamine neurons in the substantia nigra. Peripheral immune cell infiltration and activation of microglia and astrocytes are observed in PD, a process called neuroinflammation. Neuroinflammation is a fundamental response to protect the brain but, when chronic, it triggers neuronal damage. In the last decade, central and peripheral inflammation were suggested to occur at the prodromal stage of PD, sustained throughout disease progression, and may play a significant role in the pathology. Understanding the pathological mechanisms of PD has been a high priority in research, primarily to find effective treatments once symptoms are present. Evidence indicates that early life exposure to neuroinflammation as a consequence of life events, environmental or behaviour factors such as exposure to infections, pollution or a high fat diet increase the risk of developing PD. Many studies show healthy habits and products that decrease neuroinflammation also reduce the risk of PD. Here, we aim to stimulate discussion about the role of neuroinflammation in PD onset and progression. We highlight that reducing neuroinflammation throughout the lifespan is critical for preventing idiopathic PD, and present epidemiological studies that detail risk and protective factors. It is possible that introducing lifestyle changes that reduce neuroinflammation at the time of PD diagnosis may slow symptom progression. Finally, we discuss compounds and therapeutics to treat the neuroinflammation associated with PD.


The effects of exterior boundary conditions on a internally heated tumor tissue with a thermoporoelastic model.
Modeling flow field in tumor regions interstitial space is of primary importance, because of the importance of advection in macromolecule drug delivery. Its deformation has also to be taken into account because of the forces caused by the fluid; if the tumor region is not isothermal, this deformation can be also strongly affected by temperature fields. In this paper, the effects of thermal boundary conditions on a tumor region periphery with an internal heat source are investigated. The tumor region is modeled as a deformable sphere, in which two phases can be distinguished. The fluid phase is the interstitial fluid, while the rest of the tumor is modeled as the solid phase, including also capillaries and tissues. Transient-state governing equations for mass, momentum and energy are written for both phases, by also considering tumor deformation under the linear elastic material assumption. A situation of Tumor Blood Flow (TBF) rapid decay, in which vascular pressure rapidly approaches to zero, is considered, while the heat source is modeled as a fourth-grade radial-decay function. Boundary conditions for the energy equation are varied on the external surface of the sphere, in order to appreciate the effects of the surrounding on flow and temperature fields inside the tumor. After scaling equations, a finite-element scheme is employed for the numerical solution. Comparisons with analytical solutions from literature show a good agreement. Results are shown for different dimensionless parameters that are referred to temperature, volumetric strain, pressure and velocity, showing in which case external boundary conditions strongly affect tumor region flow fields and a third-kind boundary condition is needed.


Trichinella spiralis: identification and purification of superoxide dismutase.
A metalloprotein with superoxide dismutase activity was isolated and purified from muscle-stage Trichinella spiralis. The anti-genicity of the purified enzyme was demonstrated by an immunospecific reaction with T. spiralis antiserum in an enzyme-linked immunosorbent assay. In addition to its presence in somatic extracts of T. spiralis, the enzyme was also excreted into culture fluids in which the muscle-stage larvae had been incubated for periods as short as 3 hr and up to 72 hr. The enzyme was characterized as a copper- and zinc-containing, cyanide-sensitive, superoxide dismutase with a molecular weight of 36,000 (estimated by get filtration), consisting of two subunits of 17,000 Mr (estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis). The isoelectric point was 5.6. Muscle-stage T. spiralis contained one molecular form of the enzyme, whereas adult T. spiralis contained two molecular forms. This enzyme may function as an essential defense mechanism against the highly destructive superoxide radical encountered either intracellularly, as a product of biological oxidation, or externally, as a component of the host's immune system.


Structure-activity relationships of BDB and its monomethyl and dimethyl derivatives.
The purpose of the present study was to evaluate the behavioral effects of 3,4-methylenedioxyphenyl-2-butanamine (BDB), N-methyl BDB (MBDB), and N,N-dimethyl BDB (MMBDB) in the newly hatched chicken. The primary amine, BDB, produced effects that are commonly seen in the chicken after administration of both hallucinogens and psychomotor stimulants (i.e., distress vocalization, tremor, and wing extension). It also produced abnormal body posture and bursting forward locomotion, effects elicited only by hallucinogens. Loss of righting reflex also occurred at the highest (16 mg/kg) dose of BDB, and this effect is typical of d-amphetamine but has not been reported for hallucinogens. The monomethylated derivative of BDB, MBDB, was less potent than BDB, and the N,N-dimethyl analogue of BDB, MMBDB, had no effect on behavior at the doses tested.


Neural activities in v1 create a bottom-up saliency map.
The bottom-up contribution to the allocation of exogenous attention is a saliency map, whose neural substrate is hard to identify because of possible contamination by top-down signals. We obviated this possibility using stimuli that observers could not perceive, but that nevertheless, through orientation contrast between foreground and background regions, attracted attention to improve a localized visual discrimination. When orientation contrast increased, so did the degree of attraction, and two physiological measures: the amplitude of the earliest (C1) component of the ERP, which is associated with primary visual cortex, and fMRI BOLD signals in areas V1-V4 (but not the intraparietal sulcus). Significantly, across observers, the degree of attraction correlated with the C1 amplitude and just the V1 BOLD signal. These findings strongly support the proposal that a bottom-up saliency map is created in V1, challenging the dominant view that the saliency map is generated in the parietal cortex.


A retroviral vector suitable for ultrasound image-guided gene delivery to mouse brain.
Gene transfer to the early-stage embryonic brain using the ultrasound image-guided gene delivery (UIGD) technique has proven to be valuable for investigating brain development. Thus far, this technology has been restricted to the study of embryonic neurogenesis. When this technique is designed to be employed for the study in adult animals, a long-term stable gene expression will be required. We attempted to develop a retroviral vector suitable for expressing exogenous genes in the brains of postnatal and adult mice in the context of the UIGD technique. Retroviral vectors containing four different long terminal repeats (LTRs) (each from Moloney murine leukemia virus (MoMLV), murine stem cell virus (MSCV), myeloproliferative sarcoma virus (MPSV) and spleen focus-forming virus (SFFV)) were compared using the well-known CE vector having the EF1α internal promoter as a control. The MS vector containing MSCV LTR produced a higher viral titer and a higher level of gene expression than other vectors including CE. The MS vector drove the gene expression in cultured neural stem cells for 3 weeks. Furthermore, the MS vector could efficiently deliver the gene to the mouse central nervous system, as transgene expression was found in various regions of the brains and spinal cords as well as in all major neural cell types. The data from an in vivo luciferase imaging analysis showed that the gene expression from the MS vector was sustainable for almost 3 months. Our data suggested that the MS vector would be suitable to construct mice containing the transgene expressed in the brain or spinal cord in a quick and cost-effective manner.


Grants to states for operation of qualified high risk pools. Final rule.
This rule finalizes the interim final rule with comment period that was published on July 27, 2007, regarding extended funding for seed and operational grants for State High Risk Pools under the Public Health Service Act.


Serial CT studies of a metastatic pinealoma with reference to the radiotherapeutic problems.
Serial CT studies performed for 1 year on a female patient suffering from a pinealoma are reported. Under cobalt therapy (5000 rads) a remission of the pinealoma was achieved. A short time later, metastases developed and cobalt therapy was repeated (6000 rads). Rapid tumor remission was seen again, but rapid occurrence of probable metastases too. The question whether radionecrosis or metastases were present cannot be answered.


Mediation analysis shows that a decline in self-efficacy mediates the increase in fatigue severity following an initial positive response to cognitive behavioural therapy in Q fever fatigue syndrome.
Q fever fatigue syndrome (QFS) is characterized by chronic fatigue following acute Q fever. Previously, it was shown that cognitive behavioural therapy (CBT), and not doxycycline, was significantly more effective than placebo in reducing fatigue severity in QFS patients. However, this effect was not maintained after one year. The aim of this study is to elucidate the cognitive and behavioural variables which mediate the positive effect of CBT on fatigue during the treatment and the relapse of fatigue after completion of CBT, by using multiple mediation analysis. Additional analyses were performed on data of a randomized controlled trial that investigated the efficacy of CBT and antibiotics compared to placebo for QFS [1]. Only those patients in the CBT group who completed the allocated CBT treatment, and those patients in the medication group who did not follow additional CBT during follow-up, were included in this study. Two mediation models were tested, using respectively assessments at baseline and end-of-treatment (EOT), and EOT and follow-up, comparing the CBT group (n = 43) with the medication group (n = 89). During treatment, the decrease in fatigue brought on by CBT was completely mediated by an increase in self-efficacy with respect to fatigue. A reduction in self-efficacy partly mediated the increase in fatigue at follow-up in the CBT group. Given the decline in self efficacy, booster sessions focussing on restoration and maintenance of self-efficacy with respect to fatigue, may lead to elongation of the initial positive effects of CBT for QFS.


Gradient elution in micellar liquid chromatography. I. Micelle concentration gradient.
Gradient elution in micellar liquid chromatography (MLC) is discussed. On the basis of the gradient elution theory, first developed by Snyder, equations were derived for the prediction of gradient retention times in micelle concentration gradient from isocratic data. Likewise, partition coefficients into micelles and stationary phase, and subsequently isocratic retention at different micelle concentrations can be estimated from two gradient runs. However, more studies need to be done to achieve better agreement between isocratic and gradient data. The equations will be useful for efficient development of practical separations by MLC.


Comparative de novo transcriptome analysis and random UV mutagenesis: application in high biomass and astaxanthin production enhancement for Haematococcus pluvialis.
Astaxanthin is a natural carotenoid with strong antioxidant capacity. The high demand on astaxanthin by cosmetic, food, pharmaceutical and aquaculture industries promote its value in the biotechnological research. Haematococcus pluvialis Flotow 1844 has been characterized as one of the most promising species for natural astaxanthin biosynthesis. Even though H. pluvialis as an advantage in producing astaxanthin, its slow grow-yield limits usage of the species for large-scale production. In this study we generated mutated H. pluvialis strain by using one-step random UV mutagenesis approach for higher biomass production in the green flagellated period and in turn higher astaxanthin accumulation in red stage per unit algae harvest. Isolated mutant strains were tested for the astaxanthin accumulation and yield of biomass. Among tested strains only mutant strain designated as only MT-3-7-2 showed a consistent and higher growth pattern, the rest had shown a fluctuated and then decreased growth rate than wild type. To demonstrate the phenotypical changes in MT-3-7-2 is associated with transcriptome, we carried out comparative analysis of transcriptome profiles between MT-3-7-2 and the wild type strains. De novo assembly was carried out to obtain the transcripts. Differential expression levels for the transcripts were evaluated by functional annotation analysis. Data showed that increased biomass for the MT-3-7-2 strain was different from wild type with expression of transcripts upregulated in carbohydrate metabolism and downregulated in lipid metabolisms. Our data suggests a switching mechanism is enrolled between carbohydrate and lipid metabolism to regulate cell proliferation and stress responses.


Decomposition mechanism of 3-N-morpholinosydnonimine (SIN-1)--a density functional study on intrinsic structures and reactivities.
Selected intrinsic aspects of the mode of action of 3- N-morpholinosydnonimine (SIN-1) and its follow-up products are investigated by means of density functional theory. Besides the well known radical-cationic Feelisch-Schoenafinger pathway, an alternative anionic route via a neutral radical is proposed and included in the study. The individual reaction pathways are followed. Most notably, the overall activation barrier for the cationic route is calculated to be 184.04 kcal mol(-1), while the one for the anionic route is predicted to be more favorable with 14.09 kcal mol(-1).


[Physiology and biochemistry of streptomycetes. IX. Hydrolysis of cyclohexyl, carbohydrate-and aryl-esters by a carboxyl-esterase from cultures of Streptomyces hygroscopicus JA 6599].
Carboxylesterase in cell-free extracts of Streptomyces hygroscopicus was characterized with cyclohexylacetate and beta-penta-acetyl-D-glucose as as substrates. After concentrating the enzyme, activity with alpha/beta-methyl-4-O-propionyl-L-mycarosid as substrate was also observed. The influence of enzyme effectors was studied. Esterase activity was also found in the culture filtrate of. S. hygroscopicus.


Toxicity of S-pentachlorobutadienyl-L-cysteine studied with isolated rat renal cortical mitochondria.
The subcellular mechanism of alkenyl halide S-conjugate-induced nephrotoxicity was studied in mitochondria isolated from rat kidney cortex in vitro using the cysteine conjugate of hexachloro-1,3-butadiene, i.e., S-pentachlorobutadienyl-L-cysteine (PCBC) as a model substrate. Respiring mitochondria exposed to various concentrations of PCBC exhibited a dose-dependent loss of ability to retain calcium. This phenomenon was associated with a sudden collapse of the mitochondrial membrane potential. PCBC caused a slow nonenzymatic depletion of mitochondrial glutathione. This was not due to oxidation or formation of mixed disulfides, and was efficiently counteracted by preincubation with aminooxyacetic acid, an inhibitor of cysteine-conjugate beta-lyase activity. PCBC inhibited state 3 respiration in the presence of succinate as substrate, which indicates that the activity of succinate dehydrogenase was affected. Thus, the present data confirm that impairment of mitochondrial function is a feature of nephrotoxicity mediated by alkenyl halide S-conjugates. We suggest a pathway involving interaction of beta-lyase-dependent reactive metabolite with the mitochondrial inner membrane, loss of membrane potential, disturbance of Ca2+ homeostasis, and subsequent respiratory insufficiency as a mechanism for renal tubular cytotoxicity.


The prevalence of dextropropoxyphene in autopsy blood samples.
The prevalence of dextroproxyphene (DXP) in the total medico-legal autopsy material in Sweden during 1992 to 1996 was examined. Simultaneous findings of paracetamol and alcohol in the blood were considered in the analyses. DXP in peripheral blood was found in 1782 (7.5%) of the 23,691 cases analysed during 1992-1996. The autopsy prevalence of DXP increased by 25% from 1992 to 1996. The mean blood DXP concentration was 1.62 micrograms/g (the blood level of DXP after a therapeutic dose is 0.05-0.75 microgram/g). The blood DXP level was < 0.75 microgram/g in 947 cases and > or = 0.75 microgram/g in 835 cases. The cases < 50 years of age had a significantly higher mean concentration (2.36 micrograms/g) than those > or = 50 years (1.04 micrograms/g). Paracetamol in the blood was found in 53% of the DXP cases (mean 75.0 micrograms/g; therapeutic level 2.5-25 micrograms/g) and alcohol in 43% (mean level 0.14%). According to the death certificates 54% (956) died from fatal poisoning. Among these, 74% (707) showed a blood DXP concentration > or = 0.75 microgram/g. Other Scandinavian countries, Denmark and Norway have reduced the rate of fatal DXP poisonings through government regulations for prescription. As the defined daily dose/1000 inhabitants during a 12-month period (DDD) of DXP preparations in Sweden (14.4 in 1996) is six times as high as in Denmark and nine times as high as in Norway, introduction of similar regulations in Sweden should be considered.


Effects on Mycobacterium avium replication in normal human macrophages by deferiprone (L1) and other iron chelators. Possible implications on toxicity.
Mycobacterium avium growth in cultured human macrophages is influenced by serum lipids, transferrin and iron levels. Iron-saturated transferrin enhances M. avium growth, whereas apotransferrin inhibits mycobacterial replication. The ability of iron chelators to mimic the effects of transferrin on intracellular and extracellular M. avium growth was examined. Smooth, transparent, AIDS patient derived M. avium 7497 scrovar 4 was used to infect 7-day cultured human macrophages. Growth was measured by determining the colony-forming units (CFU) after infected macrophages were lysed 0 to 7 days after infection. The new iron chelating drug deferiprone (1,2-dimethyl-3-hydroxypyrid-4-one or L1, CAS 30652-11-0), 1-ethyl-2-methyl-3-hydroxypyrid-4-one (L1NEt), 1-propyl-2-methyl-3-hydroxypyrid-4-one (L1NPr), 1-allyl-2-methyl-3-hyproxypyrid-4-one (L1NAll), and 3,4-dihydroxycinnamic acid enhanced intracellular and extracellular mycobacterial replication at concentrations of 0.1-2.5 micrograms/ml. 2-Pyridinecarboxaldehyde-2-quinolylhydrazone (PCQH) inhibited intracellular replication from 0.1-1.0 microgram/ml. Most, but not all of the PCQH-induced intracellular inhibition could be eliminated using iron at concentrations greater than 1.0 microgram/ml. Iron also suppressed the effects of PCQH on extracellular M. avium replication. These results indicate that iron chelators may have variable effects at different concentrations and can significantly alter both intracellular and extracellular M. avium replication. It is suggested that at low concentrations deferiprone and other aketohydroxypyridine chelators could enhance the growth of M. avium but at high concentrations may function as adjunct therapy with other antimicrobials against infections with M. avium. These findings are important for therapeutic considerations and dose protocol design in relation to the new iron chelating drug deferiprone, which is currently used in thalassaemia and other iron loaded patients, some of whom are suffering from AIDS.


Astragaloside IV inhibits oxidative stress-induced mitochondrial permeability transition pore opening by inactivating GSK-3β via nitric oxide in H9c2 cardiac cells.
This study aimed to investigate whether astragaloside IV modulates the mitochondrial permeability transition pore (mPTP) opening through glycogen synthase kinase 3β (GSK-3β) in H9c2 cells. H9c2 cells were exposed to astragaloside IV for 20 min. GSK-3β (Ser(9)), Akt (Ser(473)), and VASP (Ser(239)) activities were determined with western blot. The mPTP opening was evaluated by measuring mitochondrial membrane potential (ΔΨ(m)). Nitric oxide (NO) generation was measured by 4-amino-5-methylamino-2', 7'-difluorofluorescein (DAF-FM) diacetate. Fluorescence images were obtained with confocal microscopy. Astragaloside IV significantly enhanced GSK-3β phosphorylation and prevented H(2)O(2)-induced loss of ΔΨ(m). These effects of astragaloside IV were reversed by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, the NO sensitive guanylyl cyclase selective inhibitor ODQ, and the PKG inhibitor KT5823. Astragaloside IV activated Akt and PKG. Astragaloside IV was also shown to increase NO production, an effect that was reversed by L-NAME and LY294002. Astragaloside IV applied at reperfusion reduced cell death caused by simulated ischemia/reperfusion, indicating that astragaloside IV can prevent reperfusion injury. These data suggest that astragaloside IV prevents the mPTP opening and reperfusion injury by inactivating GSK-3β through the NO/cGMP/PKG signaling pathway. NOS is responsible for NO generation and is activated by the PI3K/Akt pathway.


Abdominal epilepsy in an adolescent with bilateral perisylvian polymicrogyria.
We report a patient with recurrent episodes of severe periumbilical pain accompanied by headache, pallor, dizziness, and visual hallucinations who was subsequently diagnosed as having abdominal epilepsy and a bilateral sylvian cortical malformation. During an EEG examination, the patient had a simple partial seizure, manifested as intense abdominal pain. The ictal EEG showed a focal electrographic seizure arising from the left frontotemporal region. Computed tomography scan was normal; however, magnetic resonance imaging (MRI) revealed asymmetric lesions involving both sylvian fissures compatible with polymicrogyria. Onset of treatment with sodium valproate was followed by a significant reduction of seizures. Abdominal epilepsy should be suspected in adolescents or adults with paroxysmal episodes of abdominal pain associated with migraine-like symptoms. EEG and MRI investigations are indicated. A developmental brain disorder should be considered as a possible etiology.


Novel prognostic implications of complement activation in the tumour microenvironment for de novo metastatic BRAF V600E mutant colorectal cancer.
Prognosis of metastatic BRAF V600E mutant colorectal cancer (CRC) is poor, and the prognostic implications of immune contextures in the tumour microenvironment (TME) for CRC remain elusive. We collected the primary tumour specimens and clinicopathological characteristics of patients with de novo metastatic microsatellite-stable BRAF V600E mutant CRC from two medical centres. Gene expression analysis was performed using the nCounterⓇ PanCancer Immune Profiling Panel. The Cox proportional hazards regression model was used for analysing survival outcomes in association with immune gene expression and immune cells. Our complement score was defined on the basis of the average gene expression in the selected co-expression module. High expression of classical and regulatory complement genes was significantly associated with poor prognosis (N = 54). A high complement score (defined as a score above the median value) indicated significantly shorter survival. The overall survival (OS) impact of the high score remained significant in multivariate analyses. Additionally, our complement score was strongly correlated with C4d expression in immunohistochemical staining and tumour-associated macrophage (TAM) M2 signatures. Complement activation in the TME was significantly associated with poor OS and was correlated with TAM M2 in patients with de novo metastatic BRAF V600E mutant CRC.


Changes in the utilization of diagnostic codes in neonatology following the introduction of activity-based financing.
Activity-based financing was introduced in public hospitals in Norway in 1997. Following this, hospitals have been financed in part by block grants, in part by grants based on productivity as measured through weighted diagnosis-related groups (DRGs). Insufficient national data were available to allow for proper calculation of DRG weights for neonatology. Thus, data from other countries were used to estimate weights. It seemed of interest to examine whether the use of diagnostic codes in neonatal medicine was changed following the introduction of activity-based financing and DRGs. Data from 1994, 1996, 1998, and 2000 were obtained from the proprietary database of the NICU at Rikshospitalet, University of Oslo, as well as from the hospital Patient Information Management System. Diagnoses were organized into 39 categories, counted for each of the 4 years, and analyzed by non-parametric ANOVA. There were significant changes in the use of diagnostic categories during the 1994-2000 time period. Some diagnoses which previously have been only rarely used, became more frequent. The use of other diagnoses varied in ways that could only be understood in terms of tactical usage. It is concluded that the use of DRGs as a basis for activity-based financing may result in changes in the use of certain diagnostic categories which are not related to biological changes in the patient population. This may complicate epidemiological research. On the other hand, activity-based financing may result in increased attention to the diagnostic process, leading to increased use of secondary diagnoses and thus more complete diagnostic coding.


Optical resolution of n-butyl D- and L-lactates using immobilized lipase catalyst.
n-Butyl D- and L-lactates (BuDLa and BuLLa) were incubated with immobilized lipase. (1)H-NMR showed that BuDLa reacted to oligomers, while BuLLa did not react. A mixture containing 90.4% of BuLLa and 9.6% of BuDLa was incubated with the enzyme for 72 h, then distilled. The purity of BuLLa increased to 98.6%.


Methyl 3-((6-methoxy-1,4-dihydroindeno[1,2-c]pyrazol-3-yl)amino)benzoate (GN39482) as a tubulin polymerization inhibitor identified by MorphoBase and ChemProteoBase profiling methods.
A series of indenopyrazoles was synthesized from the corresponding indanones and phenyl isothiocyanates in two steps. Among the compounds synthesized, methyl 3-((6-methoxy-1,4-dihydroindeno[1,2-c]pyrazol-3-yl)amino)benzoate 6m (GN39482) was found to possess a promising antiproliferative activity toward human cancer cells without affecting any antimicrobial and antimalarial activities at 100 nM. Both a methoxy group at R(1) position and a methoxycarbonyl group at R(2) position of the anilinoquinazoline framework are essential for the high cell growth inhibition. Both MorphoBase and ChemProteoBase profiling analyses suggested that compound 6m was classified as a tubulin inhibitor. Indeed, compound 6m inhibited the acetylated tubulin accumulation and the microtubule formation and induced G2/M cell cycle arrest in HeLa cells, revealing that a promising antiproliferative activity of compound 6m toward human cancer cells is probably caused by the tubulin polymerization inhibition.


Studies on the antitumor 2,6-piperazinediones: synthesis of 2,3-diacetoxy-4-carbomethoxy-(3',5'-dioxo-N4' substituted piperazinyl methyl) benzene.
The title compounds having the structure of 2,3-diacetoxy-4-carbomethoxy-(3',5'-dioxo-N4'-substituted piperazinyl methyl) benzene were synthesized from 2-hydroxy-3-methoxybenzaldehyde in eight steps. Compound 9h showed a potent inhibitory effect against P388 leukemia cells in vitro.


Fluorine detected 2D NMR experiments for the practical determination of size and sign of homonuclear F-F and heteronuclear C-F multiple bond J-coupling constants in multiple fluorinated compounds.
The use of fluorine in molecules obtained from chemical synthesis has become increasingly important within the pharmaceutical and agricultural industry. NMR characterization of these compounds is of great value with respect to their structure elucidation, their screening in metabolomics investigations and binding studies. The favorable NMR properties of the fluorine nucleus make NMR with fluorine detection of great value in this respect. A suite of NMR 2D F-F- and F-C-correlation experiments with fluorine detection was applied to the assignment of resonances, (n)J(CF)- and (n)J(FF)-couplings as well as the determination of their size and sign. The utilization of this experiment suite was exemplarily demonstrated for a highly fluorinated vinyl alkyl ether. Especially F-C HSQC and J-scaled F-C HMBC experiments allowed determining the size of the J-couplings of this compound. The relative sign of its homo- and heteronuclear couplings was achieved by different combinations of 2D NMR experiments, including non-selective and F2-selective F-C XLOC, F2-selective F-C HMQC, and F-F COSY. The F2-one/two-site selective F-C XLOC versions were found highly useful, as they led to simplifications of the common E.COSY patterns and resulted in a higher confidence level of the assignment by using selective excitation. The combination of F2-one/two-site selective F-C XLOC experiments with a F2-one-site selective F-C HMQC experiment provided the signs of all (n)J(CF)- and (n)J(FF)-couplings in the vinyl moiety of the test compound. Other combinations of experiments were found useful as well for special purposes when focusing for example on homonuclear couplings a combination of F-F COSY-10 with a F2-one-site selective F-C HMQC could be used. The E.COSY patterns in the spectra demonstrated were analyzed by use of the spin-selective displacement vectors, and in case of the XLOC also by use of the DQ- and ZQ-displacement vectors. The variety of experiments presented shall contribute to facilitate the interpretation of F-C correlations as well as to open alternative pathways for the determination of size and signs of homo- and heteronuclear couplings of multiply fluorinated small molecules.


Chemical and genetic similarity and diversity of Ligularia anoleuca and L. fischeri collected in the Hengduan Mountains of China.
The sesquiterpenoid composition in the root and the DNA sequences of evolutionarily neutral regions were studied in Ligularia anoleuca and Ligularia fischeri (Asteraceae) collected in the Sichuan Province of China. LC-MS analysis showed that L. anoleuca populations from different localities had different chemical compositions. However, the isolated compounds were similar to each other, indicating that the differences in chemical composition were not large. The DNA analysis suggested that the two species were indistinguishable. Seventeen furanoeremophilanes and an eremophilane acetal were isolated.


Comparison of the biological properties of purified natural and recombinant human interleukin-2.
We compared the biological properties of the purified recombinant human IL-2 derived from E. coli with those of purified natural IL-2. Both had almost the same specific in vitro activities on a weight basis to support long-term proliferation of IL-2 dependent human peripheral blood lymphocytes, a mouse killer T cell line, and a mouse natural killer cell line; induce killer cells in normal mouse spleen cells; and induce antibody forming cells in nude mouse spleen cells. No differences in these biological activities were found between two forms of natural IL-2 that were separable by reverse phase high performance liquid chromatography.


The expanded mesh free gingival graft: A novel approach to increase the width of keratinized mucosa.
The importance of an adequate amount of peri-implant keratinized tissue and attached mucosa has recently been emphasized. This manuscript presents preliminary findings of a novel approach for increasing the width of keratinized mucosa (KM) around dental implants using a mesh free gingival graft (mesh-FGG). Two healthy adults were treated as part of this study. After implant placement, a large edentulous alveolar ridge with shallow vestibule and minimal amount of KM was treated in both subjects (one in the posterior mandible and the other in the anterior mandible) with the combination of an apically positioned flap and a mesh-FGG. Clinical, esthetic and patient-reported outcomes were observed at approximately 4-month time points. All sites healed uneventfully after the treatments. In both cases, increased vestibule depth, soft-tissue thickness, and width of peri-implant KM were obtained. The patients did not report any accessory discomfort. Four months following the grafting procedure, good overall esthetic outcome was observed with minimal color disparity and graft demarcation. Width of KM around dental implants can be increased using a mesh-FGG. Randomized controlled clinical studies comparing mesh-FGG to conventional FGG and other commonly applied techniques are required to assess the long-term efficacy of this novel technique in terms of soft-tissue thickness, width of peri-implant KM, and patient-reported outcomes. Principal Findings: Meshed-FGG allowed an expansion of the length of the harvested graft. This results in coverage of large recipient sites, increase in height of KM and good aesthetic integration of the graft.


[Congenital dyserythropoietic anemia type II with novel mutations in SEC23B and HFE2 genes: a Chinese family survey].
To report novel mutations SEC23B gene in congenital dyserythropoietic anemia (CDA). By direct sequencing method, we sequenced CDAN1 and SEC23B genes in a Chinese CDA II patient, presented with chronic fatigue and dark urine, as well as his family members. Serum hepcidin was assayed by mass spectrometry. We found a c.71G>A mutation and a c.74C> A mutation in the patient. In addition, a heterozygous c.55A>G mutation of HFE2 gene was found in some family members. The level of serum hepcidin of the patient was below the detection limit (<1 nmol/L). Contrary with what have been reported previously in the Europe, especially in the Italy, the gene mutations identified in this case was different and novel. The two novel mutations contribute to the diagnosis of CDAII and are the first report in East Asian CDAII patients.


[Evolution of nutritional status, immunological and virological parameters in children with vertically transmitted HIV under antiretroviral treatment]
continuous growth monitoring allows the identification of anthropometric and metabolic disorders as an integral part of HIV treatment. It was proposed to analyze the evolution of nutritional status, with the immunological and virological parameters in children infected with vertically transmitted HIV and its association with highly active antiretroviral treatment (HAART). were included 56 children aged 0 to 12 years, attending the Hospital Materno Neonatal of Córdoba, Argentina between 1998-2014. Anthropometric and biochemical, immunological, virological nutritional status and clinical manifestations were evaluated by age group (younger or older than 6 years) and HAART administered in three medical controls. in the third control the analysis of the anthropometric nutritional status according to the body mass index (BMI) diagnosed 47 children (83.93%) with a normal BMI and 6 (10.71%) overweight/obesity, without statistically significant difference by age group (p=0.10). Thirty six children (64.29%) presented hypertriglyceridemia, with higher concentrations at the second (p=0.003) and third control (p=0.06) in those treated with scheme II and III with protease inhibitors (PI), unlike scheme I without IP. Normoglycemia prevailed in 54 children (96.43%) and anemia in 29 (51.79%). The clinical manifestations decreased in the successive controls and in the last one, 3 children (5.36%) older than 6 years, had pneumonia and one (1.79%) severe immunosuppression. hypertriglyceridemia was the main adverse effect of the medication, which, added to the high prevalence of anemia, constitute important parameters for interdisciplinary treatment


Granulocyte-macrophage colony-stimulating factor to increase efficacy of mitoxantrone, etoposide and cytarabine in previously untreated elderly patients with acute myeloid leukaemia: a Swedish multicentre randomized trial.
A total of 110 patients, aged 64 years or over, with de novo acute myeloid leukaemia (AML) and white blood cell counts <50 x 109/l were treated with 3 d of cytarabine 1 g/m2 twice daily, mitoxantrone 12 mg/m2 and etoposide 200 mg/m2, randomized with or without the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) 200 microg/m2. The primary aim was to evaluate the effect of GM-CSF on the remission rate. Secondary aims included comparison of duration of remission, survival and infectious complications and the impact of maintenance therapy with thioguanine. Complete remission (CR) was achieved by 64% of patients without GM-CSF, and by 65% of patients who received GM-CSF, the median remission duration was 13 vs. 6 months, the median overall survival (OS) was 14 vs. 9 months, the mean time to neutrophil recovery was 25 vs. 17 d (P = 0.03) and the number of positive blood cultures was 46 vs. 39 (P = 0.05) respectively. The impact of thioguanine remains unanswered since only 30 patients remained in CR after consolidation therapy. We conclude that induction therapy is feasible with acceptable toxicity in elderly patients with AML, albeit with a high relapse rate and short OS. GM-CSF prior to, and in combination with, induction treatment reduced the time to neutrophil recovery and the number of neutropenic septicaemia cases but did not improve the OS of AML in the elderly.


Ultrashort pulse coherence properties in coherent linear amplifiers.
We examine coherence properties of small-area, intrinsically stationary statistical pulses propagating in amplifying media in the vicinity of an optical resonance. Any such medium acts as a coherent linear amplifier, amplifying and reshaping the pulse. We show that an initially nearly incoherent Gaussian Schell-model pulse becomes almost fully coherent and its state of coherence becomes nearly uniform across the temporal profile as the pulse propagates into the amplifying medium.


Second-trimester cervical sonography: features other than cervical length to predict spontaneous preterm birth.
To estimate whether cervical and lower uterine segment characteristics other than cervical length and funneling predict recurrent preterm birth. We conducted a secondary analysis of a multicenter, blinded observational study of 181 women with singletons and prior spontaneous preterm births. Endovaginal ultrasonic examinations were performed at 2-week intervals between 16 0/7 weeks and 23 6/7 weeks of gestation. Cervical canal contour (straight/curved), cervical position (horizontal/vertical), posterior cervical width, lower uterine segment thickness, vascularity, endocervical canal dilation, with or without associated membrane prolapse and chorioamnion visible at the internal os, were systematically assessed. At the initial sonogram (16 0/7-18 6/7 weeks), membranes visible overlying the internal os (relative risk 1.9, confidence interval [CI] 1.2, 3.1) and canal dilation of 2-4 mm (relative risk 2.6, CI 1.4, 4.7) were significant predictors of spontaneous preterm birth of less than 35 weeks in univariate analyses. Only canal dilation remained statistically significant after controlling for cervical length (odds ratio 5.5, CI 1.1, 28.6). Endocervical canal dilation of 2-4 mm during second-trimester endovaginal sonography was associated with an increased risk of recurrent preterm delivery independent of cervical length. II-2


Educational differences in US parents' time spent in child care: The role of culture and cross-spouse influence.
We explore effects of parents' education on how much time they spend in child care, using a sample of married and cohabiting parents from the 2003 to 2011 American Time Use Study. We find that more educated parents spend more time in child care, despite having higher employment rates. For men, there is some mixed evidence that their own education increases their child care time, but much stronger evidence that their child care time is influenced by their wives' education. For women, it is largely their own education affecting their child care time. We also assess whether the higher earnings of the well educated, which could be used to outsource housework, explains why they spend more time in child care. Results do not support this hypothesis; educational differences do not change much under controls for his and her earnings or housework. This suggests that the effects of education on child care result from different cultural conceptions of child rearing held by the well educated, especially by women, whose education affects both their own and their husbands' child care time.


Intervention to Improve Diarrhea-Related Knowledge and Practices Among Informal Healthcare Providers in Slums of Kolkata.
In the densely populated slums of Kolkata, informal healthcare providers' (IHP) diarrhea-related knowledge and rationality of practices should be improved to reduce risk of adverse outcome, expenditure, and antimicrobial resistance. A multicomponent intervention was conducted among 140 representative IHPs in the slums of 8 wards in Kolkata to assess its impact on their diarrhea-related knowledge and practice. Six intervention modules in local languages were provided (1 per month) with baseline (N = 140) and postintervention (N = 124) evaluation. Mean overall (61.1 to 69.3; P < .0001) and domain-specific knowledge scores for etiology/spread (5.4 to 8.1; P < .0001), management (6.4 to 7.2; P < .0001), and oral rehydration solution ([ORS] 5.7 to 6.5; P < .0001) increased significantly (at α = 0.05) after intervention and were well retained. Impact on knowledge regarding etiology/spread (adjusted odds ratio [aOR] = 5.6; P < .0001), cholera (aOR = 2.0; P = .0041), management (aOR = 3.1; P < .0001), ORS (aOR = 2.3; P = .0008), and overall (aOR = 4.3; P < .0001) were significant. Intervention worked better for IHPs who practiced for ≥10 years (aOR = 3.2; P < .0001), untrained IHPs (aOR = 4.8; P < .0001), and pharmacists (aOR = 8.3; P < .0001). Irrational practices like empirical antibiotic use for every cholera case (aOR = 0.3; P < .0001) and investigation for every diarrhea case (aOR = 0.4; P = .0003) were reduced. Rationality of testing (aOR = 4.2; P < .0001) and antibiotic use (aOR = 1.8; P = .0487) improved. Multicomponent educational intervention resulted in sustainable improvement in diarrhea-related knowledge and practices among IHPs in slums of Kolkata. Policy implications should be advocated along with implementation and scale-up.


Retrospective study of apremilast drug survival in psoriasis patients in a daily practice setting: A long-term experience.
There is limited evidence about the real-world survival of apremilast in patients with psoriasis, especially over the long term. To evaluate the long-term survival of apremilast and its predictive factors when used to treat psoriasis. A retrospective hospital-based study, including data collected from 104 patients. Survival curves were estimated using the Kaplan-Meier estimator. Proportional hazard Cox regression models were used for multivariate analysis. The average duration of the treatment before discontinuation was 28.82 months (95% CI, 22.08-35.57 months) and the median was 12 months (95% CI, 2.68-21.31 months). The retention rates were 51% (1 year), and 33% (5 years). The survival study revealed statistically significant differences between patients with PASI<10 and those in the PASI≥10 group (log-rank test, p < 0.001). The 5-year prevalences were 64% for patients with a PASI of <10 and 5% for those with an index ≥10. In the PASI < 10-patient group, the retention rates were 77% (1 year) and 64% (5 years). Furthermore, 66% of patients who continued apremilast treatment for more than 2 years were receiving off-label doses (30 mg/day). Apremilast may be a suitable and efficient alternative for the treatment of psoriasis patients in the PASI<10 group.


Purification and characterization of tissue kallikrein-like proteinases from the black sea bass (Centropristis striata) and the southern frog (Rana berlandieri).
Serine proteinases were isolated from the pyloric caeca of the black sea bass (Centropristis striata) and the pancreas of the Southern frog (Rana berlandieri) and were purified to apparent homogeneity by aprotinin affinity column chromatography, reverse phase high performance liquid chromatography and gel filtration FPLC liquid chromatography to produce products with molecular masses of approximately 27,000 Da and isoelectric points from 4.2 to 5.0. Both enzymes were kallikrein-like and were bound by diisopropylfluorophosphate; had pH optima from 9 to 10; showed high specificity for the hydrolysis of arginine peptide bonds and low to moderate affinity for lysine bonds at the P1 substrate recognition sites; were inhibited by aprotinin, benzamidine, leupeptin, and soybean trypsin inhibitor; generated kinin from kininogen and were highly stable at room temperature. Differences between the enzymes were observed relative to their hydrophobicities, substrate specificities, stabilities at acidic pHs in the presence and absence of calcium, and the amounts of kinin generated from kininogen. Many of the fish trypsins, previously identified as anionic trypsins, may actually be more kallikrein-like.


Head-to-Head Intra-Individual Comparison of Biodistribution and Tumor Uptake of [18F]FAPI-74 with [18F]FDG in Patients with PDAC: A Prospective Exploratory Study.
Radiolabeled fibroblast activation protein (FAP) ligands, a novel class of tracers for PET/CT imaging, have demonstrated very promising results in various oncological, as well as in some benign, diseases with long-term potential to supplant the current pan-cancer agent [18F]FDG in some cancer types. Pancreatic ductal carcinoma (PDAC) belongs to the group of epithelial malignancies with a strong so-called "desmoplastic reaction", leading to a prominent tumor stroma with cancer-associated fibroblasts that exhibit a marked overexpression of fibroblast activation protein (FAP). The first clinical experiences in PDAC with 68Ga-labeled FAP ligands suggested superior sensitivity to [18F]FDG. However, there is limited data with 18F-labeled FAP derivatives, i.e. [18F]FAPI-74, yet prospective single- and multicenter trials are already ongoing. In this proof-of-concept study, we sought to evaluate the biodistribution, tumor uptake, and lesion detectability in patients with PDAC using [18F]FAPI-74 PET/CT as compared to [18F]FDG PET/CT scans for staging. This study includes 7 patients (median age 69) who underwent both [18F]FDG PET/CT with contrast-enhancement and [18F]FAPI-74 PET with low-dose CT for primary staging (n = 3) and therapy response control after neoadjuvant (n = 1) or re-staging after palliative therapy (n = 3). The mean interval between PET scans was 11 ± 4 days (range 1-15 days). The [18F]FDG and [18F]FAPI-74 PET/CT scans were acquired at 64 ± 4.1 min (range 61-91 min) and 66.4 ± 6.3 min (range 60-76 min), respectively, after administration of 200 ± 94 MBq (range 79-318 MBq) and 235 ± 88 MBq (range 90-321 MBq), respectively. Quantification of tracer uptake was determined with SUVmax and SUVmean. Furthermore, the tumor-to-background ratio (TBR) was derived by dividing the SUVmax of tumor lesions by the SUVmax of adipose tissue, skeletal muscle, and blood pool. Overall, 32 lesions were detected in 7 patients including primary (n = 7), lung (n = 7), bone (n = 3), lymph node (n = 13), and peritoneal metastases (n = 2). [18F]FAPI-74 detected 22% more lesions compared with [18F]FDG with a better TBR and visual lesion delineation. In one patient the primary lesion could be detected unequivocally with [18F]FAPI-74 but was missed by [18F]FDG imaging. Altogether, most of the lesions demonstrated markedly elevated uptake of [18F]FAPI-74 with a simultaneous lower uptake in the background, providing a very high visual contrast. To the best of our knowledge, this is the first, prospective, intra-individual investigation comparing [18F]FAPI-74 with [18F]FDG imaging in PDAC with encouraging results. These pivotalresults supporta larger, multicentric, prospective study to determine the value of [18F]FAPI-74 in detecting and staging PDAC in comparison with current standard of care imaging.


Performance of an atlas-based autosegmentation software for delineation of target volumes for radiotherapy of breast and anorectal cancer.
To validate atlas-based autosegmentation for contouring breast/anorectal targets. ABAS uses atlases with defined CTVs as template cases to automatically delineate target volumes in other patient CT-datasets. Results are compared with manually contoured CTVs of breast/anorectal cancer according to RTOG-guidelines. The impact of using specific atlases matched to individual patient geometry was evaluated. Results were quantified by analyzing Dice Similarity Coefficient (DSC), logit(DSC) and Percent Overlap (PO). DSC >0.700 and logit(DSC) >0.847 are acceptable. In addition a new algorithm (STAPLE) was evaluated. ABAS produced good results for the CTV of breast/anorectal cancer targets. Delineation of inguinal lymphatic drainage, however, was insufficient. Results for breast CTV were (DSC: 0.86-0.91 ([0,1]), logit(DSC): 1.82-2.36 ([-∞,∞]), PO: 75.5-82.89%) and for anorectal CTVA (DSC: 0.79-0.85, logit(DSC): 1.40-1.77, PO: 68-73.67%). ABAS produced satisfactory results for these clinical target volumes that are defined by more complex tissue interface geometry, thus streamlining and facilitating the radiotherapy workflow which is essential to face increasing demand and limited resources. STAPLE improved contouring outcome. Small target volumes not clearly defined are still to be delineated manually. Based on these results, ABAS has been clinically introduced for precontouring of CTVs/OARs.


A systematic review of hearing and vestibular function in carriers of the Pro51Ser mutation in the COCH gene.
The Pro51Ser (P51S) COCH mutation is characterized by a late-onset bilateral sensorineural hearing loss (SNHL) and progressive vestibular deterioration. The aim of this study was to carry out a systematic review of all reported hearing and vestibular function data in P51S COCH mutation carriers and its correlation with age. Scientific databases including Medline, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, ISI Web of Knowledge, and Web of Science were searched to accumulate information about hearing outcome and vestibular function. Eleven genotype-phenotype correlation studies of the P51S COCH variant were identified and analyzed. The SNHL starts at the age of 32.8 years. The Annual Threshold Deterioration is 3 decibel hearing loss (dB HL) per year (1-24 dB HL/year). Profound SNHL was observed at 76 years on average (60-84 years). 136 individual vestibular measurements were collected from 86 carriers. The onset of the vestibular dysfunction was estimated around 34 years (34-40 years), and vestibular deterioration rates were higher than those of the SNHL, with complete bilateral loss observed between 49 and 60 years. Both audiometric and vestibular data were processed with much different methodologies and pre-symptomatic P51S carriers were systematically underrepresented. Further delineation of this correlation would benefit cross-sectional and longitudinal study involving all (pre-symptomatic and symptomatic) P51S carriers.


SAPHO syndrome in an adolescent: a clinical case with unusual severe systemic impact.
SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome includes both dermatological and rheumatologic symptoms. Being a rare condition, the diagnosis is frequently late. The authors report a case of a 13-year-old boy diagnosed with synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome with unusual severe systemic repercussions. The patient presented with acne conglobata, inability to walk due to pain and weakness and weight loss. Bone scintigraphy was suggestive of sacroiliitis, and lumbar spine x-ray showed signs of hyperostosis. His clinical state improved after treatment with nonsteroidal anti-inflammatory drugs, methotrexate, clindamycin, and isotretinoin. A review of the clinical aspects of this syndrome is presented, emphasizing how this underdiagnosed syndrome can lead to severe weight loss and significant functional and psychological impairment at an early age.


Hepatitis B serology--help in interpretation.
This review discusses the serologic markers of hepatitis B virus (HBV) infection. Interpretation of various serologic profiles is provided, and the importance of maternal screening for interruption of perinatal transmission of HBV infection is stressed.


Carcinoma of the larynx in a child.
Squamous cell carcinoma of the larynx in children is a rare entity, only 21 cases have been reported in patients 10-years-old or younger. A 9-year-old girl presented because of dyspnea and mild hoarseness of one week duration. Laryngoscopy and bronchoscopy showed a supraglottic mass, which proved to be poorly differentiated squamous cell carcinoma. No neck nodes or systemic metastasis were present. The tumor regressed with radiation therapy (6400 rads) but local recurrence and lung metastasis were evident 6 weeks later. Chemotherapy was refused by the parents and the patient died in one month. It is believed that squamous cell carcinoma of the larynx in children parallels that of adults in many respects including response to treatment. However, our attempt to save the larynx by avoiding surgery and using radiotherapy alone was not successful. Squamous cell carcinoma of the larynx in children may be more aggressive than that of adults. The scarcity of cases impedes establishment of treatment protocols in children. Initial aggressive management using surgery, radiotherapy, and possibly chemotherapy may be warranted in children.


Automated Dispensing Cabinet Overrides Should be Considered Risky, Not Routine.
The safety organization ECRI has listed overriding of safety controls in automated dispensing cabinets as one of the top 10 health technology hazards of 2023.Overrides contribute to medication errors and can harm patients, sometimes fatally. Nurses should only consider using an override in extreme emergencies.


Analytical techniques for characterization of raw materials in cell culture media.
Raw materials are a critical part of any cell culture medium; therefore, it is of utmost importance to understand and characterize them for high-quality product. The raw material characterization (RMC) program at SAFC focuses on individual screening of raw materials both analytically and biologically. The goal of the program is to develop the best-in-class knowledge base of the raw materials used in SAFC's media formulations and their impact on performance of products.


Design, synthesis and biological evaluation of novel evodiamine and rutaecarpine derivatives against phytopathogenic fungi.
Evodiamine and rutaecarpine are two alkaloids isolated from traditional Chinese herbal medicine Evodia rutaecarpa, which have been reported to have various biological activities in past decades. To explore the potential applications for evodiamine and rutaecarpine alkaloids and their derivatives, various kinds of evodiamine and rutaecarpine derivatives were designed and synthesized. Their antifungal profile against six phytopathogenic fungi Rhizoctonia solani, Botrytis cinerea, Fusarium graminearum, Fusarium oxysporum, Sclerotinia sclerotiorum, and Magnaporthe oryzae were evaluated for the first time. Furthermore, a series of modified imidazole derivatives of rutaecarpine were synthesized to investigate the structure-activity relationship. The results of antifungal activities in vitro showed that imidazole derivative of rutaecarpine A1 exhibited broad-spectrum inhibitory activities against R. solani, B. cinerea, F. oxysporum, S. sclerotiorum, M. oryzae and F. graminearum with EC50 values of 1.97, 5.97, 12.72, 2.87 and 16.58 μg/mL, respectively. Preliminary mechanistic studies showed that compound A1 might cause mycelial abnormalities of S. sclerotiorum, mitochondrial distortion and swelling, and inhibition of sclerotia formation and germination. Moreover, the curative effects of compound A1 were 94.7%, 81.5%, 80.8%, 65.0% at 400, 200, 100, 50 μg/mL in vivo experiments, which was far more effective than the positive control azoxystrobin. Significantly, no phytotoxicity of compound A1 on oilseed rape leaves was observed obviously even at a high concentration of 400 μg/mL. Therefore, compound A1 is expected to be a novel leading structure for the development of new antifungal agents.


Preventive effect of gliclazide on experimental atherosclerosis in rabbits.
Administration of a hypoglycaemic sulphonamide, gliclazide, at 10 mg/kg/day p.o. to rabbits for 60 days did not affect the development of plasma lipid disturbances induced by a high cholesterol diet. The accumulation of cholesterol in the liver was significantly reduced by up to 34% when compared with animals on the high cholesterol diet. The high concentrations of glycerides and fatty acids in the aorta were significantly decreased towards normal values and histology showed that the gliclazide strongly inhibited the development of aortic and particularly coronary lesions induced by the atherogenic diet. A normal appearance of coronary arteries was noted in more than 50% of cases.


Effects of elevated yolk androgens on perinatal begging behavior in yellow-legged gull (Larus michahellis) chicks.
Maternal hormones may represent an important pathway by which mothers can adaptively adjust offspring traits and performance to suit the prevailing environmental conditions. Earlier studies of birds have shown that egg androgens of maternal origin may enhance post-natal offspring 'begging' displays, functioning to solicit parental care. Here we investigate the effects of elevated egg androgen levels on the prenatal begging behavior of yellow-legged gull (Larus michahellis) chicks. At laying, we experimentally increased the concentration of yolk testosterone (T) within the natural range of variation, and, shortly before hatching, we compared the structural properties, rate, and loudness of vocalizations of embryos developing in T- and oil-injected (control) eggs. In addition, we compared the early post-hatch begging rate (measured as the pecking rate towards a dummy gull head) in chicks of the two experimental groups. We found that T embryos produced louder embryonic vocalizations than controls, whereas structural properties and the calling rate did not differ between T and control embryos. The post-hatch begging rate was unaffected by T treatment, but strongly decreased with increasing chick body mass, suggesting that intensity of the begging display was sensitive to chick state and may therefore reliably indicate the need of food in this species. Therefore, the results of this study show for the first time that prenatal T exposure modulates the quality of embryonic vocalizations, but are not in accordance with previous findings reporting increased post-hatching begging intensity following increased prenatal exposure to androgens.


Familial cardiological and targeted genetic evaluation: low yield in sudden unexplained death and high yield in unexplained cardiac arrest syndromes.
It has been reported that cardiological screening and genetic evaluation in relatives of families with sudden unexplained death syndrome and unexplained cardiac arrest (UCA) may uncover a heritable etiology in a significant proportion of families. To evaluate the yield of a comprehensive evaluation protocol of a large unselected cohort of consecutive families with autopsy-negative sudden unexplained death syndrome (termed sudden arrhythmic death syndrome [SADS]) and UCA. We studied (1) 109 consecutive families (411 relatives) referred with 1 or more sudden deaths in the family and (2) 52 consecutive probands with UCA (91 relatives) referred by cardiologists between January 2007 and December 2012. A comprehensive cardiological screening was performed followed by targeted genetic evaluation if a clinical phenotype was proven or suspected. Diagnosis was made by a multidisciplinary team using published clinical criteria. A diagnosis was made in 19 of 109 families with SADS (yield 18%), with the majority having long QT syndrome (LQTS). Diagnosis varied according to proband age, with LQTS most common in the very young (≤20 years) and Brugada syndrome in the older age probands (≥40 years) (P = .03). In contrast, a diagnosis was made in 32 of 52 families with UCA (yield 62%), the majority of which had LQTS and Brugada syndrome. No clinical or circumstantial factors increased the likelihood of diagnosis in families with either SADS or UCA. In contrast to previously published series, a comprehensive strategy of cardiological evaluation and targeted genetic testing in more than 100 families with SADS was found to have a lower diagnostic yield (18%). Diagnostic yield in families with UCA was approximately 4 times higher (62%), which is consistent with the published literature.


Synthesis of alpha-amyrin derivatives and their in vivo antihyperglycemic activity.
Ficus racemosa belongs to the family of Moraceae and is commonly known as 'Gular' in north India. Bio-activity guided isolation work on the fruits of F. racemosa resulted in the identification of antidiabetic active principle, alpha-amyrin acetate 7. Compound 7 lowered the blood glucose levels by 18.4 and 17.0% at 5 and 24 h, respectively, in sucrose challenged streptozotocin induced diabetic rat (STZ-S) model at the dose of 100 mg/kg body weight. Fifteen novel derivatives viz, 9-21, 24, 25 of alpha-amyrin 8 were prepared and their antihyperglycemic activity profile was assessed. The p-chlorobenzoic acid derivative 9 and nicotinic acid derivative 14 showed potent antihyperglycemic activity at 100 mg/kg body weight.


Characterization of a range of fura dyes with two-photon excitation.
Two-photon excitation (TPE) spectra of Fura-2, -4F, -6F, -FF, and Furaptra were characterized using a tunable (750-850 nM) ultra-short pulse laser. Two-photon fluorescence of these dyes was studied in free solution and in the cytosol of isolated rabbit ventricular cardiomyocytes. The TPE spectra of the Ca(2+)-free and Ca(2+)-bound forms of the dyes were measured in free solution and expressed in terms of the two-photon fluorescence cross section (Goppert-Meyer units). The Fura dyes displayed the same Ca(2+)-free TPE spectrum in the intracellular volume of permeabilized and intact cardiomyocytes. Fluorescence measurements over a range of laser powers confirmed the TPE of both Ca(2+)-free and Ca(2+)-bound forms of the dyes. Single-wavelength excitation at 810 nM was used to determine the effective dissociation constants (K(eff)) and dynamic ranges (R(f)) of Fura-2, -4F, -6F, -FF, and Furaptra dyes (K(eff) = 181 +/- 52 nM, 1.16 +/- 0.016 micro M, 5.18 +/- 0.3 micro M, 19.2 +/- 1 micro M, and 58.5 +/- 2 micro M; and R(f) = 22.4 +/- 3.8, 12.2 +/- 0.34, 6.3 +/- 0.17, 16.1 +/- 2.8, and 25.4 +/- 4, respectively). Single-wavelength excitation of intracellular Fura-4F resolved diastolic and peak [Ca(2+)] in isolated stimulated cardiomyocytes after calibration of the intracellular signal using reversible exposure to low (100 micro M) extracellular [Ca(2+)]. Furthermore, TPE of Fura-4F allowed continuous, long-term (5-10 min) Ca(2+) imaging in ventricular cardiomyocytes using laser-scanning microscopy without significant cellular photodamage or photobleaching of the dye.


A re-evaluation of the role of type IV antifreeze protein.
A lipoprotein-like antifreeze protein (type IV AFP) has previously been isolated only from the blood plasma of the longhorn sculpin. However, the plasma antifreeze activity in all individuals of this species tested from Newfoundland and New Brunswick waters ranges from low to undetectable. A close relative of the longhorn sculpin, the shorthorn sculpin, does have appreciable antifreeze activity in its blood but this is virtually all accounted for by the alpha-helical, alanine-rich type I AFP, other isoforms of which are also present in the skin of both fishes. We have characterized a putative ortholog of type IV AFP in shorthorn sculpin by cDNA cloning. This 12.2-kDa Gln-rich protein is 87% identical to the longhorn sculpin's type IV AFP. Recombinant versions of both orthologs were produced in bacteria and shown to have antifreeze activity. Immunoblotting with antibodies raised to type IV AFP shows this protein present in longhorn sculpin plasma at levels of less than 100 microg/mL, which are far too low to protect the blood from freezing at the temperature of icy seawater. This confirms the results of direct antifreeze assays on the plasmas. It appears that type IV AFP has the potential to develop as a functional antifreeze in these fishes but may not have been selected for this role because of the presence of type I AFP. Consistent with this hypothesis is the observation that the type IV AFP gene has not been amplified the way functional antifreeze protein genes have in all other species examined.


Oestrogen and progesterone interactions in the control of gonadotrophin and prolactin secretion.
Oestrogen and progesterone have marked effects on the secretion of the gonadotrophins and prolactin. During most of the oestrous or menstrual cycle the secretion of gonadotrophin is maintained at a relatively low level by the negative feedback of oestrogen and progesterone on the hypothalamic-pituitary system. The spontaneous ovulatory surge of gonadotrophin is produced by a positive feedback cascade. The cascade is initiated by an increase in the plasma concentration of oestradiol-17 beta which triggers a surge of luteinizing hormone releasing hormone (LHRH) and an increase in pituitary responsiveness to LHRH. The facilitatory action of oestrogen on pituitary responsiveness is reinforced by progesterone and the priming effect of LHRH. How oestrogen and progesterone exert their effects is not clear but the facilitatory effects of oestrogen take about 24 h, and the stimulation of LHRH release is produced by an indirect effect of oestradiol on neurons which are possibly opioid, dopaminergic or noradrenergic and which modulate the activity of LHRH neurons. In the rat, a spontaneous prolactin surge occurs at the same time as the spontaneous ovulatory gonadotrophin surge. The prolactin surge also appears to involve a positive feedback between the brain-pituitary system and the ovary. However, the mechanism of the prolactin surge is poorly understood mainly because the neural control of prolactin release appears to be mediated by prolactin inhibiting as well as releasing factors, and the precise role of these factors has not been established. The control of prolactin release is further complicated by the fact that oestradiol stimulates prolactin synthesis and release by a direct action on the prolactotrophes. Prolactin and gonadotrophin surges also occur simultaneously in several experimental steroid models. A theoretical model is proposed which could explain how oestrogen and progesterone trigger the simultaneous surge of LH and prolactin.


The C-terminal region of the alpha subunit of Escherichia coli RNA polymerase is required for transcriptional activation of the flagellar level II operons by the FlhD/FlhC complex.
A number of transcription activators have been found to activate transcription via protein-protein contact between RNA polymerase alpha subunits and transcription factors; they are classified as class I factors. In this report, we demonstrate that the FlhD/FlhC complex, a transcription activator of the Escherichia coli flagellar regulon, requires the C-terminal domain of the RNA polymerase alpha subunit for transcription activation. We conclude that FlhD/FlhC is a class I transcription factor.


Comparative quantitative electrophysiologic effects of adenosine triphosphate on the sinus node and atrioventricular node.
A pharmacologic approach was used to characterize the sinus node (SN) and atrioventricular (AV) node responses to intravenous adenosine triphosphate (ATP) in 21 patients during electrophysiologic testing. ATP produced dose-dependent prolongation of spontaneous sinus cycle length. The mean maximal increase in sinus cycle length was 294 +/- 60 ms (n = 10). The mean dose of ATP required to produce this maximal sinus cycle length prolongation was 3.5 +/- 1.0 mg. The dose-response curve for sinus cycle length prolongation was sigmoid in shape with an EC50 of 0.39 mg derived from a median effect plot. There was a negative correlation between the control sinus cycle length and the dose of ATP required to produce the maximal prolongation of cycle length (p less than 0.05). In contrast, the mean dose of ATP producing AV block was 4.4 +/- 0.97 mg and the EC50 was 2.98 mg. There was a positive correlation between the AV nodal functional refractory period and the prolongation of the AH interval with a 2 mg dose (p less than 0.05). Consistent with the AV nodal dose-response curves, 8 mg ATP terminated paroxysmal reentrant supraventricular tachycardia at the AV node in 8 of 9 patients. Thus, SN and AV node responses to ATP have differences in their electrophysiologic correlates and EC50. These findings suggest that ATP has potentially different mechanisms of action on SN automaticity and AV nodal conduction that requires further investigation.


Calculation of the NMR second moment for materials with different types of internal rotation.
The measurements of the NMR second moment can reveal information about structural and dynamical details of the sample providing that analysis of the experimental results on the basis of the Van Vleck's formula can be performed. In this paper the method of calculating the Van Vleck's second moment for solids with complex internal motions is presented. The method is based on simulating any desired motion of atoms within a block of unit cells large enough to reflect the property of the macroscopic sample and calculating the second moment value averaged by this motion. The detailed description of this method is given for the case of rotation of molecules or groups of atoms. The algorithm of the computer program which performs calculation based on the described method is also presented. Examples of application of the described method are listed.


cDNA sequence analysis of the main olive allergen, Ole e I.
Olea europaea (Ole e) I-specific cDNA sequences were amplified by 3'-RACE-PCR, using specific primers based on the N-terminal sequence of the allergen, and cloned into appropriate vectors. The nucleotide sequence data obtained revealed the presence of isogenic variation in Ole e I gene(s). The molecular mass, pI, amino acid composition and sequence of the predicted polypeptides agree with data previously obtained by analysis of purified Ole e I from pollen. Furthermore, by treatment of purified Ole e I with specific glycopeptide hydrolases it has been demonstrated the presence of N-glycosylation in the allergen, and there is a unique concensus site for N-linked glycosylation at positions 111-113 of the deduced amino acid sequence. The Ole e I predicted sequence shows a significant homology with three putative proteins encoded respectively by the another-specific LAT52 gene from tomato and the pollen specific genes Zmc13 from maize and OSPSG from rice, suggesting that these proteins could have a role in one of the development processes unique to male gametophytes.


Increased prevalence of insomnia and changes in hypnotics use in England over 15 years: analysis of the 1993, 2000, and 2007 National Psychiatric Morbidity Surveys.
To investigate changes over 15 years in the prevalence of insomnia and its association with demographic characteristics and hypnotic medication use. Analysis of 3 cross-sectional national mental health surveys carried out in 1993, 2000, and 2007, which used comparable sampling methods and identical insomnia assessments. Adults living in private households in England. 20,503 people aged 16-64 years. Insomnia was defined according to 4 different criteria, using relevant questions from the revised Clinical Interview Schedule. Modest increases in insomnia prevalence were found over the survey periods (any symptoms increasing from 35.0% in 1993 to 38.6% in 2007; insomnia diagnosis from 3.1% to 5.8%, respectively). In all 3 surveys, similar strengths of association in relation to all criteria were found, with female gender, increased age, lower educational attainment, depression, unemployment, economic inactivity, and widowed, divorced, or separated status. Prevalence of hypnotic use was double in 2000 (0.8%) compared to 1993 (0.4%); from limited information on selected medications, there was no such increase between 2000 and 2007. The reasons reported for any sleep disturbance over the last month were generally similar across surveys, the most marked change being illness/discomfort increasing as an explanation from 14.3% to 17.4% to 19.0%. In the English general population, insomnia (by any definition) showed a modest but steady increase in prevalence over a 15-year period. Strengths of associations with demographic factors and self-reported reasons for sleep disturbance remained reasonably stable over this period.


Trace Elements in Breakfast Cereals and Exposure Assessment in Moroccan Population: Case of Lead and Cadmium.
The role of breakfast cereals in a balanced diet has been recognized for many years. Such foods should be safe and not contain toxic substances, especially trace elements. Among these elements, lead (Pb) and cadmium (Cd) are two important inorganic food contaminants. In this study, we assessed the contamination levels of breakfast cereal samples available in Morocco with Pb and Cd. For this, a total of sixty-two (n = 62) samples of breakfast cereals purchased in different markets in the country were surveyed for their Pb and Cd contents by using atomic absorption spectrophotometer (GF-AAS) after total mineralization of samples. Results showed that out of 62 total samples, 47 samples (75.8%) were contaminated with Pb concentrations in the range of 0.016-1.057 μg/g. The remaining samples (24.2%) were under the detection limit (LOD) of Pb. In the case of Cd, 41 samples (66.1%) were contaminated with Cd levels that ranged between 0.011 and 0.123 μg/g. In the present study, four samples (6.45%) of breakfast cereals are above the maximum limit (0.2 μg/g) set by the European Commission Regulation No 1881/2006 for Pb in cereals. However, for the Cd, only one sample exceeded the maximum limit set for this element (0.1 μg/g). The levels compare well with those reported worldwide for similar foodstuffs. The estimation of the provisional weekly intakes of the two elements (Pb and Cd) showed that the risks of development of toxicological effects through breakfast cereals are very low. However, it is important that the long-term exposure to these elements be kept to minimum. This is the first study on the co-occurrence of the two trace elements (Pb and Cd) in breakfast cereal samples commercialized in Morocco.


Neuroimaging for patient selection for medial temporal lobe epilepsy surgery: Part 1 Structural neuroimaging.
The objective of part one of this review is to present the structural neuroimaging techniques that are currently used to evaluate patients with temporal lobe epilepsy (TLE), and to discuss their potential to define patient eligibility for medial temporal lobe surgery. A PubMed query, using Medline and Embase, and subsequent review, was performed for all English language studies published after 1990, reporting neuroimaging methods for the evaluation of patients with TLE. The extracted data included demographic variables, population and study design, imaging methods, gold standard methods, imaging findings, surgical outcomes and conclusions. Overall, 56 papers were reviewed, including a total of 1517 patients. This review highlights the following structural neuroimaging techniques: MRI, diffusion-weighted imaging, tractography, electroencephalography and magnetoencephalography. The developments in neuroimaging during the last decades have led to remarkable improvements in surgical precision, postsurgical outcome, prognosis, and the rate of seizure control in patients with TLE. The use of multiple imaging methods provides improved outcomes, and further improvements will be possible with future studies of larger patient cohorts.