A prospective study of carbohydrate intake and risk of all-cause and specific-cause mortality.
To investigate the associations between carbohydrate intake and the risk of overall and specific-cause mortality in a prospective cohort study. Diet was measured using 24 h dietary recalls. Underlying cause of death was identified through linkage to the National Death Index. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression. During a median follow-up of 7.1 years among 35,692 participants who aged 20-85 years, a total of 3854 deaths [783 cardiovascular disease (CVD)-specific and 884 cancer-specific death] were identified. Carbohydrate intake was not associated with risk of overall mortality (multivariable-adjusted HR comparing extreme quartiles 1.03, 95% CI 0.94, 1.13, ptrend = 0.799), while higher fiber intake was associated with lower mortality risk (HR 0.86, 95% CI 0.77, 0.95, ptrend = 0.004). Replacing 5% of energy from carbohydrate with both plant fat and plant protein was associated with 13% (95% CI 8%, 17%) and 13% (95% CI 3%, 22%) lower risk of total and CVD mortality, respectively. Whereas a positive or null association was found when replacing carbohydrate with both animal fat and animal protein. Higher carbohydrate-to-fiber ratio was associated with increased risk of overall (HR 1.20, 95% CI 1.09, 1.33, ptrend < 0.001) and cancer-specific (HR 1.17, 95% CI 0.95, 1.44, ptrend = 0.031) mortality. Our findings suggested that high fiber diet or diet with low carbohydrate-to-fiber ratio was associated with lower long-term death risk, and provided evidence for the health benefit from dietary substitution of both plant fat and plant protein for carbohydrate.


A prospective cohort study of the combined effects of physical activity and anthropometric measures on the risk of post-menopausal breast cancer.
Although keeping a healthy weight and being physically active are among the few modifiable risk factors for post-menopausal breast cancer, the possible interaction between these two risk factors remains to be established. We analyzed prospectively a cohort of 19,196 women who provided detailed self-report on anthropometric measures, physical activity and possible confounders at enrollment in 1997. We achieved complete follow-up through 2010 and ascertained 609 incident cases of post-menopausal invasive breast cancer. We calculated metabolic energy turnover (MET h/day) per day and fitted Cox proportional hazards models to estimate hazard ratios (HRs) with 95 % confidence intervals (CIs). The incidence of post-menopausal breast cancer among obese women (BMI ≥ 30 kg/m(2)) was 58 % higher (HR 1.58, CI 1.16-2.16) than in women of normal weight (18.5 ≤ BMI < 25). Women in the lowest tertile of total physical activity (< 31.2 MET h/day) had 40 % higher incidence of post-menopausal breast cancer (HR 1.40, CI 1.11-1.75) than those in the highest tertile (≥ 38.2 MET h/day). The excess incidence linked to these two factors seemed to combine in an approximately additive manner; the incidence among the most obese and sedentary women was doubled (HR 2.07, CI 1.31-3.25) compared with the most physically active women with normal weight. No heterogeneity of the physical activity-linked risk ratios across strata of BMI was detected (p value for interaction = 0.98). This prospective study revealed dose-dependent, homogenous inverse associations between post-menopausal breast cancer incidence and physical activity across all strata of BMI, and between post-menopausal breast cancer incidence and BMI across all strata of physical activity, with no evidence of additive or multiplicative interaction between the two, suggesting independent effects.


New opportunities and novel paradigms to support neuromuscular research.
This article provides an overview of the structure and function of the National Skeletal Muscle Research Center (NSMRC) at the University of California, San Diego, which is one of the 7 research centers of the Medical Rehabilitation Research Infrastructure Network, created to facilitate access for physicians to experts, technology, and resources from scientific fields related to medical rehabilitation. The 4 cores of the NSMRC are described as a resource for rehabilitation medicine practitioners to use for clinically relevant muscle research.


Micro-electron diffraction structure of the aggregation-driving N terminus of Drosophila neuronal protein Orb2A reveals amyloid-like β-sheets.
Amyloid protein aggregation is commonly associated with progressive neurodegenerative diseases, however not all amyloid fibrils are pathogenic. The neuronal cytoplasmic polyadenylation element binding protein is a regulator of synaptic mRNA translation and has been shown to form functional amyloid aggregates that stabilize long-term memory. In adult Drosophila neurons, the cytoplasmic polyadenylation element binding homolog Orb2 is expressed as 2 isoforms, of which the Orb2B isoform is far more abundant, but the rarer Orb2A isoform is required to initiate Orb2 aggregation. The N terminus is a distinctive feature of the Orb2A isoform and is critical for its aggregation. Intriguingly, replacement of phenylalanine in the fifth position of Orb2A with tyrosine (F5Y) in Drosophila impairs stabilization of long-term memory. The structure of endogenous Orb2B fibers was recently determined by cryo-EM, but the structure adopted by fibrillar Orb2A is less certain. Here we use micro-electron diffraction to determine the structure of the first 9 N-terminal residues of Orb2A, at a resolution of 1.05 Å. We find that this segment (which we term M9I) forms an amyloid-like array of parallel in-register β-sheets, which interact through side chain interdigitation of aromatic and hydrophobic residues. Our structure provides an explanation for the decreased aggregation observed for the F5Y mutant and offers a hypothesis for how the addition of a single atom (the tyrosyl oxygen) affects long-term memory. We also propose a structural model of Orb2A that integrates our structure of the M9I segment with the published Orb2B cryo-EM structure.


A radiographic comparison of prehospital cervical immobilization methods.
Three methods of prehospital cervical immobilization were studied radiographically and compared to the short board technique (SBT). The methods were California Stif-Neck Immobilizing Collar (CSC), Kendrick Extrication Device (KED), and Extrication Plus-One (XP-One). Forty-five volunteers were immobilized in the short board (SB) and one of the test devices studied. Cervical movement in the sagittal and frontal planes was measured radiographically. Movement in the horizontal plane was measured directly. Two-tailed, paired t test analysis was performed comparing test devices to the SBT. The SBT proved to be significantly better (P less than .05) in the following comparisons: the CSC in extension and lateral bending; the KED in lateral bending; and the XP-One in extension. We confirm the SBT as the standard of comparison against which newer prehospital devices can be compared objectively. Of the three devices compared against the SBT, the factory-fabricated short board devices (KED and XP-One) provided the greatest degree of immobilization, in addition to logistical advantages over the SBT.


Development of self-efficacy of newly graduated registered nurses in an aged care program.
To evaluate an aged care program in developing self-efficacy of newly graduated registered nurses. An evaluation of the program was conducted using a mixed methods approach. Twenty-four nurses completed the pre- and post-survey of aged care nursing self efficacy and attended one of three focus groups held to gain in-depth understanding of their insight into the program. There was an increase in nurses' self-efficacy post-program. The increased self-efficacy and new knowledge gained enhanced nurses' confidence and enabled them to critically appraise their workplace practices. The improved confidence resulting from increased self-efficacy and new knowledge gained from the aged care program enabled nurses to critically appraise the practices in their workplace, demonstrating the program's effectiveness. Aged care service providers should support continuing education for aged care nurses to ensure sustainability of a competent workforce to manage the increasing aged care population.


The amylase-producing microflora of semi-preserved canned sausages: identification of the bacteria and characterization of their amylases.
Thirteen strains of amylase-producing bacteria were isolated from semi-preserved canned sausages and their ingredients. All belonged to the genus Bacillus, and could be separated into 4 different groups. Two groups were different strain of B. subtilis, one was B. amyloliquefaciens and the last was B. macerans. The identification of the different bacteria species was supported by disc gel electrophoresis of the supernatant culture fluid, after growth. The amylases were characterized with regard to temperature optimum, pH optimum and thermostability. Although some of the amylases appear to be quite thermostable, the only explanation for starch degradation in semi-preserved foods seems to be the amylase production from outgrowing spores which survived the heat treatment.


Influenza vaccination in caregivers of childhood cancer survivors.
An increased risk of influenza-related morbidity and mortality in childhood cancer survivors could be significantly reduced through vaccinations. This study aimed to examine influenza vaccination practices by caregivers of childhood cancer survivors. Study subjects were 364 caregivers, recruited at three major hospitals in South Korea. We collected demographic and medical information through self-administered questionnaires, along with clinical information of childhood cancer survivors by reviewing medical records. Multiple logistic regression analysis was performed to analyze factors associated with influenza vaccination of caregivers. A total of 55.2% of caregivers had received influenza vaccination at least once and 24.2% had received yearly influenza vaccinations during the last 3 years. Caregivers with highest education level were more likely to receive influenza vaccination than caregivers with lowest education level: aOR (95% CI) was 3.42 (1.17, 9.99) for ever-receipt of vaccination and 3.33 (1.15, 9.58) for yearly vaccination. One-year increase in caregiver age was inversely associated with ever-receipt of vaccination (aOR (95% CI), 0.94 (0.90, 0.98)) as well as yearly vaccination (aOR (95% CI), 0.92 (0.88, 0.97)). Increasing time lapse since the end of treatment was also associated with lower vaccinations. Influenza vaccination rates of childhood cancer survivor caregivers were suboptimal. Time lapse after completing cancer treatment, caregiver age, and educational level were independently associated with receipt of influenza vaccination by caregivers. To promote influenza vaccination in caregivers of childhood cancer survivors to prevent influenza-related morbidity and mortality in childhood cancer survivors is necessary.


Micropurification and amino acid sequence of beta-casomorphin-8 in milk from a woman with postpartum psychosis.
Milk was obtained from a woman with acute postpartum psychosis and with ongoing lactation. Defatted samples were subjected to micropurification and collected fractions were analyzed by means of their beta-casomorphin-8 immunoreactivity. Immunoreactive material with the same chromatographic properties as synthetic human beta-casomorphin-8 was determined by amino acid sequence analysis to be Tyr-Pro-Phe-Val-Glu-Pro-Ile-Pro. Its molecular mass was determined by fast atom bombardment-mass spectrometry to be 962.3 Da. These determinations, which ultimately identify the immunoreactive material as human beta-casomorphin-8, represent the first structural identification of a beta-casomorphin peptide from a body fluid.


2D atomic crystal molecular superlattices by soft plasma intercalation.
Two-dimensional (2D) atomic crystal superlattices integrate diverse 2D layered materials enabling adjustable electronic and optical properties. However, tunability of the interlayer gap and interactions remain challenging. Here we report a solution based on soft oxygen plasma intercalation. 2D atomic crystal molecular superlattices (ACMSs) are produced by intercalating O2+ ions into the interlayer space using the plasma electric field. Stable molecular oxygen layer is formed by van der Waals interactions with adjacent transition metal dichalcogenide (TMD) monolayers. The resulting interlayer gap expansion can effectively isolate TMD monolayers and impart exotic properties to homo-(MoS2[O2]x) and hetero-(MoS2[O2]x/WS2[O2]x) stacked ACMSs beyond typical capacities of monolayer TMDs, such as 100 times stronger photoluminescence and 100 times higher photocurrent. Our potentially universal approach to tune interlayer stacking and interactions in 2D ACMSs may lead to exotic superlattice properties intrinsic to monolayer materials such as direct bandgap pursued for future optoelectronics.


Urbanization, migration, and indigenous health in Peru.
We compare demographic, socioeconomic, and anthropometric characteristics and blood pressure (BP), between rural and urban Peruvian indigenous women. These are preliminary results from a project on urbanization, migration, and health. Data were collected cross-sectionally (2019) and compared between a rural (n = 92) and an urban (n = 93) community. Height: μ = 148.3 ± 5.0 cm (range = 137-162), weight: μ = 62.0 ± 11.5 (range = 37.5-108.7), median waist circumference = 89.0 (IQR = 15.8, range = 64.0-126.0), BMI = 28.3 (IQR = 6.2, range = 16.7-40.0), with no significant rural-urban differences. Systolic but not diastolic BP was significantly higher in urban versus rural women (median = 110, IQR = 18, range = 80-170 vs. median = 120, IQR = 10, range = 90-170, p = .002 and median = 70, IQR = 17, range = 50-100 vs. median = 70, IQR = 10, range = 60-100, p = .354), respectively. Despite major lifestyle differences, there were no anthropometric differences between rural and urban women. Higher systolic BP in urban women may reflect social/economic stressors rather than dietary factors.


Incidence of and Risk Factors for Screw Loosening after Iliosacral Screw Fixation for Posterior Pelvic Ring Injury.
Screw loosening is a common complication of iliosacral screw fixation, with subsequent loss of stability and fracture re-displacement. This study aimed to investigate the incidence of and risk factors for screw loosening after iliosacral screw fixation for posterior pelvic ring injury. A total of 135 patients with posterior pelvic ring injuries who were treated with iliosacral screw fixation in our department between July 2015 and April 2021 were selected for this retrospective analysis. The possible risk factors for screw loosening were investigated using univariate and multivariate logistic regression analyses of patient demographics and trauma-related and iatrogenic variables, including age, sex, body mass index, Osteoporosis Self-Assessment Tool for Asians (OSTA) index, mechanism of injury, Young-Burgess classification, site of injury, type of injury, type of screw, mode of fixation, numbers of guidewire adjustments, accuracy of screw position, and quality of fracture reduction. The incidence of screw loosening was 15.6% (n = 21). The mean duration for screw loosening was 3.2 ± 1.5 months after operation. Univariate analysis results showed that the Young-Burgess classification, type of injury, site of injury, type of screw, mode of fixation, and OSTA index might be related to screw loosening (p < 0.05). According to the multivariate logistic regression, vertical shear injuries (Odds ratios [OR] 9.80, 95% Confidence intervals [CI] [1.96-73.28], p = 0.008), type of injury (OR 0.25, 95% CI [0.13-0.79], p = 0.027), common screws (OR 6.94, 95% CI [1.53-31.40], p = 0.012), screws insertion only at the level of the first sacral segment (S1) (OR 8.79, 95% CI [1.18-65.46], p = 0.034), injury site located in the medial sacral foramina (OR 6.28, 95% CI [1.16-34.06], p = 0.033), and lower OSTA index [OR 0.41, 95% CI [0.24-0.71], p = 0.001] were significantly related to screw loosening. Vertical shear injuries, sacral fractures, injury site located in the medial sacral foramina, and lower OSTA index are significantly associated with the postoperative occurrence of screw loosening. Transiliac-transsacral screw fixation and screws insertion both at the level of the S1 and second sacral segment can prevent screw loosening.


Two simple and rapid methods based on maximum diameter accurately estimate large lesion volumes in acute stroke.
We compared two simple and rapid diameter-based methods (ABC/2, od-value) in terms of their accuracy in predicting lesion volume >70 ml and >100 ml. In 238 DWI images of ischemic stroke patients from the AXIS2 trial, maximum lesion diameter and corresponding maximum orthogonal diameter were measured. Estimation of infarct volume based on od-value and ABC/2 calculation was compared to volumetric assessments. Accuracy of od-value and ABC/2 was similar for >70 ml (92.0 vs. 87.4) and >100 ml (92.9 vs. 93.3). ABC/2 overestimated lesion volume by 29.9%, resulting in a lower specificity. Od-value is a robust tool for patient selection in trials.


Operational efficiency of Asia-Pacific airports.
Airports are important drivers of economic development and thus under tremendous pressure from emerging competitors. However, few studies have analysed the operational efficiency of Asia-Pacific airports. This study therefore evaluated the operational efficiency of 21 Asia-Pacific airports between 2002 and 2011. A two-stage method was used: Data Envelopment Analysis (DEA) to assess airport efficiency, followed by the second-stage regression analysis to identify the key determinants of airport efficiency. The first-stage DEA results indicated that Adelaide, Beijing, Brisbane, Hong Kong, Melbourne, and Shenzhen are the efficient airports. The second-stage regression analysis suggested that percentage of international passengers handled by an airport, airport hinterland population size, dominant airline(s) of an airport when entering global airline strategic alliance, and an increase in GDP per capita are significant in explaining variations in airport efficiency.


Effects of bacterial agarase on agarose gel in cell culture.
Bacterial agarase, concentrated and purified from culture filtrate of agar-degrading bacteria, has been used to clean cells cultured in soft agarose from gel residues. The enzyme also has been used to liquefy the gel directly in the dishes to facilitate the removal of cells. The sufaces of glioma cells from agarase-treated colonies could not be distinguished in the scanning electron microscope from surfaces of cells which had never been in contact with agarose or agarase. This implies that most agarose residues had been removed, and also that the treatment did not seriously alter the cell surfaces. The influence of the agarase treatment also was tested by comparison of the mitotic index and the incorporation of [3H]thymidine in agarase-treated and untreated cells. No effects of the treatment could be seen in these tests.


Reduced caregiving quality measured during the strange situation procedure increases child's autonomic nervous system stress response.
Dysfunctional maternal behavior has been shown to lead to disturbances in infant's regulatory capacities and alterations in vagal reactivity. We aim to investigate the autonomic nervous system (ANS) response of the child during the strange situation procedure (SSP) in relation to the quality of maternal behavior. Twelve month after birth, 163 mother-child-dyads were investigated during the SSP. Heart rate (HR) and both, the parasympathetic branch (PNS) via the respiratory sinus arrhythmia (RSA) and the sympathetic branch (SNS) via the left ventricular ejection time (LVET) of the ANS were continuously determined during the SSP using electrocardiogram (ECG) and impedance cardiogram (ICG) measures. Maternal behavior was assessed by using the AMBIANCE measure. The ANS response in infants of mothers with disruptive behavior compared to infants of non-disruptive mothers was significantly altered during the SSP: HR increased especially when infants of disruptive mothers were alone with the stranger (F (1, 161) = 4.15, p = .04) with a significant vagal withdrawal when being in contact with the stranger despite of presence of the mother (F (1, 161) = 5.11, p = .03) and a significant increase in vagal tone during final reunion (F (1, 161) = 3.76, p = .05). HR increase was mainly based on a decrease in LVET (F (1, 161) = 4.08, p = .05) with a maximum infant's HR when the stranger came into the room instead of the mother. Both, SNS and PNS branches of the child are significantly altered in terms of an ANS imbalance, especially during contract to a stranger, in relation to dysfunctional maternal behavior. Our findings suggest the importance of supporting high quality caregiving that enables the infant to adapt adequately to stressful interpersonal situations which is likely to promote later health.


Activating and optimizing the In-Plane interface of 1 T/2H MoS2 for efficient hydrogen evolution reaction.
Implanting the octahedral phase (1 T) into the hexagonal phase (2H) of the molybdenum disulfide (MoS2) matrix is considered one of the effective methods to enhance hydrogen evolution reaction (HER) performances of MoS2. In this paper, hybrid 1 T/2H MoS2 nanosheets array was successfully grown on conductive carbon cloth (1 T/2H MoS2/CC) via facile hydrothermal method and the 1 T phase content in 1 T/2H MoS2 is regulated to gradually increase from 0 % to 80 %. 1 T/2H MoS2/CC with 75 % 1 T phase content exhibits optimal HER performances. The DFT calculation results show that S atoms in 1 T/2H MoS2 interface exhibit the lowest hydrogen adsorption Gibbs free energies (ΔGH*) compared with other sites. The improvement of HER performances are primarily attributed to activating the in-plane interface regions of the hybrid 1 T/2H MoS2 nanosheets. Furthermore, the relationship between 1 T MoS2 content in 1 T/2H MoS2 and catalytic activity was simulated by a mathematical model, which shows that the catalytic activity presents a trend of increasing and then decreasing with the increase of 1 T phase content.


Activity and growth efficiency of heterotrophic bacteria in a salt marsh (Ria de Aveiro, Portugal).
Bacterial utilization of monomers is recognized as an important step in the biogeochemical cycling of organic matter. In this study we have compared the heterotrophic activity of bacterial communities from different micro-habitats within a salt marsh environment (Ria de Aveiro, Portugal) in order to establish spatial patterns of bacterial abundance, monomer turnover rates (Tr) and bacterial growth efficiency (BGE). Differences in bacterial abundance and activity could be found between distinct plant rhizospheres. BGE tended to be lower at Halimione portulacoides banks, when compared to Sarcocornia perennis subsp. perennis banks which, on the contrary, showed the highest bacterial densities. Experiments of amendment of natural samples with organic and inorganic supplements indicated that salt marsh bacteria are not strongly regulated by salinity but the increased availability of labile organic matter causes a significant metabolic shift towards mineralization.


Conformational characteristics of peptides and unanticipated results from crystal structure analyses.
Preferred conformation and types of molecular folding are some of the topics that can be addressed by structure analysis using x-ray diffraction of single crystals. The conformations of small linear peptide molecules with 2-6 residues are affected by polarity of solvent, presence of water molecules, hydrogen bonding with neighboring molecules, and other packing forces. Larger peptides, both cyclic and linear, have many intramolecular hydrogen bonds, the effect of which outweighs any intermolecular attractions. Numerous polymorphs of decapeptides grown from a variety of solvents, with different cocrystallized solvents, show a constant conformation for each peptide. Large conformational changes occur, however, upon complexation with metal ions. A new form of free valinomycin grown from DMSO exhibits near three-fold symmetry with only three intramolecular hydrogen bonds. The peptide is in the form of a shallow bowl with a hydrophobic exterior. Near the bottom of the interior of the bowl are three carbonyl oxygens, spaced and directed so that they are in position to form three ligands to a K+, e.g., complexation can be completed by the three lobes containing the beta-bends closing over and encapsulating the K+ ion. In another example, free antamanide and the biologically inactive perhydro analogue, in which four phenyl groups become cyclic hexyl groups, have essentially the same folding of backbone and side chains. The conformation changes drastically upon complexation with Li+ or Na+. However, the metal ion complex of natural antamanide has a hydrophobic globlar form whereas the metal ion complex of the inactive perhydro analogue has a polar band around the middle. The structure results indicate that the antamanide molecule is in a complexed form during its biological activity. Single crystal x-ray diffraction structure analyses have identified the manner in which water molecules are essential to creating minipolar areas on apolar helices. Completely apolar peptides, such as membrane-active peptides, can acquire amphiphilic character by insertion of a water molecule into the helical backbone of Boc-Aib-Ala-Leu-Aib-Ala-Leu-Aib-Ala-Leu-Aib-OMe, for example. The C-terminal half assumes an alpha-helix conformation, whereas the N-terminal half is distorted by an insertion of a water molecule W(1) between N(Ala5) and O(Ala2), forming hydrogen bonds N(5)H...W(1) and W(1)...O(2). The distortion of the helix exposes C = O(Aib1) and C = O(Aib4) to the outside environment with the consequence of attracting additional water molecules. The leucyl side chains are on the other side of the molecule. Thus a helix with an apolar sequence can mimic an amphiphilic helix.


Maleate-fumarate conversion and other novel aspects of the reaction of a Co(II) maleate with pyridine and bipyridine.
Reaction of a molecular Co(II) maleate, [Co(Hmal)2(H2O)4], with pyridine yields a Co(II) fumarate, [Co(fum)(H2O)4], with a chain structure and a chiral pyridylsuccinic acid zwitter ion, (-)OOC-CH(N+C5H5)-CH2-COOH, in almost quantitative yields, while the reaction of 4,4'-bipyridine (bipy) with the Co(II) maleate, on the other hand, almost quantitatively generates a polylmeric Co(II) maleate, [Co(mal)(bipy)]n.(n/2)H2O along with the adduct of fumaric acid with bipyridine.


Elevation of Global O-GlcNAc in rodents using a selective O-GlcNAcase inhibitor does not cause insulin resistance or perturb glucohomeostasis.
The O-GlcNAc modification is proposed to be a nutrient sensor with studies suggesting that global increases in O-GlcNAc levels cause insulin resistance and impaired glucohomeostasis. We address this hypothesis by using a potent and selective inhibitor of O-GlcNAcase, known as NButGT, in a series of in vivo studies. Treatment of rats and mice with NButGT, for various time regimens and doses, dramatically increases O-GlcNAc levels throughout all tissues but does not perturb insulin sensitivity or alter glucohomeostasis. NButGT also does not affect the severity or onset of insulin resistance induced by a high-fat diet. These results suggest that pharmacological increases in global O-GlcNAc levels do not cause insulin resistance nor do they appear to disrupt glucohomeostasis. Therefore, the protective benefits of elevated O-GlcNAc levels may be achieved without deleteriously affecting glucohomeostasis.


Combined use of carbon nanotubes and ionic liquid to improve the determination of antidepressants in urine samples by liquid chromatography.
Antidepressants are widely used for the treatment of psychiatric disorders and therefore their monitoring in biological fluids is quite important taking into account that they can produce dangerous biochemical imbalances in toxic doses. A method for the determination of antidepressants in urine samples is presented using solid-phase extraction (SPE) and high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. Home-made cartridges containing 30 mg multiwall carbon nanotubes are employed for isolation of the analytes from the sample, allowing also the preconcentration of the analytes prior to the HPLC analysis. Chromatographic separation was achieved in a reversed-phase C(8) column using the ionic liquid 1-butyl-3-methylimidazolium trifluoromethanesulfonate as silanol activity suppressor, which enhances peak symmetry and chromatographic resolution. Limits of detection were 12.3 ng mL(-1) for trazodone and 90.1 ng mL(-1) for fluoxetine. The repeatability of the proposed method expressed as RSD (n = 11) varied between 3.4% (fluoxetine) and 5.0% (desipramine and mianserine). Thus, the method is suitable for the therapeutic monitoring of antidepressants in urine samples.


Hypothyroidism affects corneal homeostasis and wound healing in mice.
Thyroid hormones have a critical role in maintaining metabolic and physiological homeostasis. However, understanding of the possible effects of thyroid dysfunction on corneal homeostasis and the wound healing process is quite limited. To explore the influence of hypothyroidism on corneal homeostasis and the post-wound repair processes of the murine cornea. A hypothyroidism model was established by total thyroidectomy (TThy) in C57BL/6J mice. On day 10 after TThy, hypothyroidism was confirmed via thyronine (T3 and T4) and thyroid-stimulating hormone serum levels. We further assessed changes in corneal thickness, corneal sensitivity, sub-basal nerve density, and the corneal expression of thyroid hormone receptors. A corneal epithelial abrasion model was established via mechanical removal of a central epithelium 2 mm in diameter. Wound closure and recruitment of inflammatory cells (neutrophils and γδ T-cells) were evaluated. RNA-sequencing and gene set enrichment analysis were performed in injured corneas after abrasion. The effect of local T3 administration on corneal wound healing in thyroidectomized mice was also observed. Compared with sham-operated control mice, the TThy-treated mice showed the following: (1) a significant decrease in corneal epithelial thickness, sensitivity to external stimuli, and sub-basal nerve density, as well as an alteration in thyroid hormone receptor expression in the steady state; (2) delayed corneal wound repair and enhanced inflammatory response after corneal abrasion; (3) down-regulation of actin-skeleton and DNA replication pathways and up-regulation of inflammation-associated pathways in abraded corneas; and (4) significant restoration of delayed corneal wound repair and inhibition of excessive inflammation following topical T3 administration. We conclude that deficient thyroid hormone secretion significantly affects corneal homeostasis and post-wound repair processes. Topical T3 administration might have a potential reversal effect on delayed corneal wound repair among hypothyroid individuals.


Comparative genome-based identification of a cell wall-anchored protein from Lactobacillus plantarum increases adhesion of Lactococcus lactis to human epithelial cells.
Adhesion to host cells is considered important for Lactobacillus plantarum as well as other lactic acid bacteria (LAB) to persist in human gut and thus exert probiotic effects. Here, we sequenced the genome of Lt. plantarum strain NL42 originating from a traditional Chinese dairy product, performed comparative genomic analysis and characterized a novel adhesion factor. The genome of NL42 was highly divergent from its closest neighbors, especially in six large genomic regions. NL42 harbors a total of 42 genes encoding adhesion-associated proteins; among them, cwaA encodes a protein containing multiple domains, including five cell wall surface anchor repeat domains and an LPxTG-like cell wall anchor motif. Expression of cwaA in Lactococcus lactis significantly increased its autoaggregation and hydrophobicity, and conferred the new ability to adhere to human colonic epithelial HT-29 cells by targeting cellular surface proteins, and not carbohydrate moieties, for CwaA adhesion. In addition, the recombinant Lc. lactis inhibited adhesion of Staphylococcus aureus and Escherichia coli to HT-29 cells, mainly by exclusion. We conclude that CwaA is a novel adhesion factor in Lt. plantarum and a potential candidate for improving the adhesion ability of probiotics or other bacteria of interest.


Enterobacteria of emerging pathogenic significance from clinical cases in man and animals and detection of toads and wall lizards as their reservoirs.
A total of 416 samples comprising faecal samples from diarrhoeic cases of man, calves, sheep and goats, and urine samples from patients with urinary tract infections, were examined for the presence of enterobacteria of emerging pathogenic significance. Citrobacter freundii from 20, C. intermedius biotype-a from four, Serratia marcescens (serotype 05:H13, bactericin type 16) from one and Erwinia herbicola from two human stool samples were isolated. Only two urine samples yielded C. freundii. Citrobacter freundii was isolated from 10 and C. intermedius biotype-a from two calves. From sheep and goats, two isolates of C. freundii and three of C. intermedius biotype-a were obtained. None of these samples yielded Edwarsiella tarda or Yersinia enterocolitica. The examination of 99 toads and 145 wall lizards revealed that toads were reservoirs for C. freundii, C. intermedius biotype-a and Salmonella brijbhumi, whereas wall lizards were reservoirs for C. freundii, C. intermedius biotype-a, E. herbicola, Enterobacter cloacae and Salmonella spp. These bacteria were present in the range of 2.0 x 10(6) to 6.0 x 10(11) organisms per gram of intestinal contents. In addition, toads were carriers for Edwardsiella tarda (new serotypes 04167:H1 and 05159: non-motile). None of the toads and wall lizards proved positive for C. intermedius biotype-b (C. koseri), S. marcescens and Y. entercolitica. C. freundii, C. intermedius biotype-a, E. herbicola and S. marcescens were resistant to penicillin and erythromycin whereas E. tarda isolates were also resistant to gentamycin, neomycin, colistin and sulfamethaxazole.


Critical evaluation of the potential error in pharmacokinetic studies of using the linear trapezoidal rule method for the calculation of the area under the plasma level--time curve.
The linear trapezoidal rule method is commonly used for the estimation of the area under the plasma level-time curve. Error analyses are performed when the method is used in first-order absorption and first-order elimination kinetics in the one-compartment system. It is found that significant underestimations and overestimations in area during the absorption phase and postabsorption phase, respectively, can occur when the method is improperly used. During the exponential postabsorption phase the relative error is only a function of the ratio (n) of the time interval over the half-life of the two plasma data points in the interval. The error from the linear trapezoidal rule method at n = 0.5 is about 1%. The error increases to 15.5% and 57.1% when n is increased to 2 and 4, respectively. It is recommended that for most absorption studies the linear trapezoidal method be used for prepeak and plateau plasma data and the logarithmic trapezoidal method for postpeak plasma data.


Stigmatic inhibition of pollen grain germination-its implication for frequency distribution of seed number in pods of Leucaena leucocephala (Lam) de Wit.
Seed number per pod is negatively skewed in Leucaena leucocephala. Post-fertilisation abortion of pods does not completely explain the skewed distribution. It is shown that a pre-fertilisation regulation effectively restricts the formation of pods with less than a certain number of seeds. The regulation is rendered through the inhibition of pollen grain germination by the stigmatic fluid when the pollen grain is less than a certain critical load in the stigma. Such a control is shown to have implications in the evolution of pollen package units, generation of male gametophytic competition and the economy of packing seeds in pods.


Metabolic control and quality of life in type 1 diabetes: Do adherence, family support, and school support matter?
This study analyzed the relationship between clinical and demographic variables, family support, school support, and adherence on adolescents' metabolic control and quality of life (QoL) based on Adaptation to Chronic Disease in Childhood's model. The sample included 100 adolescents and 100 parents. Adolescents were assessed on adherence, family support, school support, and QoL. Parents were assessed on family functioning and parental coping. A path analysis was performed to assess the adequacy of the theoretical model to the sample. Daily glycemic monitoring was associated with better metabolic control and diabetes hospitalizations with worse metabolic control. The final model showed adherence, family support, school support, and family functioning having an indirect effect on the relationship between adolescence stage, number of daily glycemic monitorings, number of hospitalizations, and metabolic control/QoL. Adherence had an indirect effect on the relationship between glycemic monitoring and family and school support, suggesting that adolescents need both types of support to perform diabetes self-care tasks. QoL showed a direct effect on metabolic control revealing the importance of QoL in the design of interventions to promote metabolic control in adolescents.


Contrast-enhanced ultrasonography using Sonazoid(®) is useful for diagnosis of malignant ovarian tumors: comparison with Doppler ultrasound.
The purpose of this study was to assess the usefulness of Sonazoid(®)-enhanced ultrasonography (US) in the diagnosis of ovarian cancer in comparison with Doppler US. Twenty-five ovarian tumor patients who were scheduled to undergo surgery were recruited for this study. The day before the operation, each patient was evaluated with color and power Doppler and baseline US during intravenous infusion of Sonazoid. Each lesion was classified as "benign" or "malignant" on the basis of specific criteria for a Doppler signal or Sonazoid-enhanced pattern. The reference standard was the histology of surgically removed adnexal tumors. Twenty patients were diagnosed with malignant tumors (invasive cancer, n = 15; metastatic cancer, n = 1; borderline tumor, n = 4), and the remaining five were diagnosed with benign tumors. Sonazoid-enhanced US correctly depicted the presence or absence of intratumoral blood flow in all patients with an accuracy of 92 %. Color Doppler ultrasound depicted the malignancies with an accuracy of 64 %, and power Doppler ultrasound depicted them with an accuracy of 76 %. Our study suggests that Sonazoid-enhanced US is superior to conventional color Doppler US for the diagnosis of malignant ovarian tumors, but not to power Doppler US. The data and their interpretation in our study should be taken with some degree of caution because of the small number of subjects. Further studies involving a larger sample size would be needed to confirm these findings.


Calcium Hydride Reduction of Polycyclic Aromatic Hydrocarbons.
A molecular calcium hydride effects the two electron reduction of polyaromatic hydrocarbons, including naphthalene (E0 =-3.1 V).


Employment Outcomes for Canadian Radiation Oncology Graduates: 2020 Assessment and Longitudinal Trends.
Canadian radiation oncology (RO) trainees have experienced employment challenges after residency training. The present study was conducted to evaluate current employment trends and perform comparisons to prior reported assessments. A survey was administered to all 13 Canadian RO program directors requesting the employment status and location of their graduates during the past 3 years, and their perceptions on graduates' employment challenges. Visa trainees were excluded. Findings were compared with surveys performed in 2014, 2016, and 2018. The response rate from RO program directors was 100%. There were 77 graduates identified who completed their residency training between 2017 and 2020. All had known employment status and location. Two (17%) 2020 graduates, 16 (84%) 2019 graduates, 17 (81%) 2018 graduates, and 24 (100%) 2017 graduates had staff employment. Of the 59 graduates with staff positions, 86% were in Canada. Some graduates (28%) obtained staff or locum employment in a province other than their training program. The proportion of graduates obtaining staff positions 1 year after residency increased to 84% from 46%-48% in prior assessments. Most program directors (62%) did not perceive any difficulties with their graduates finding staff employment or trainees transferring to training programs in other disciplines owing to perceived workforce challenges. Compared with 3 prior employment outcome assessments, this study observed a higher proportion of graduates with staff positions in Canada, fewer total graduates, fewer graduates seeking staff employment or in fellowship positions, and a trend for fewer graduates seeking employment or fellowships abroad. These findings support the view that the Canadian RO job market continues to improve. Although employment challenges for newly certified, Canadian-trained radiation oncologists still exist, national corrective measures to regulate resident intake in 2011 appear to have had a positive effect on the employment outcomes of recent Canadian RO graduates.


Lysosomes of the renal cortex: heterogeneity and role in protein handling.
Rate sedimentation of the kidney cortical mitochondrial/lysosomal (ML) fraction yields two distinct classes of lysosomes: the large lysosomes or protein droplets and a heterogeneous broad band of smaller lysosomes. The protein droplets which are recovered as a well defined zone of high purity also sediment as a homogeneous band after equilibrium banding at a density of 1.235 g/ml in sucrose. The small lysosomes co-sediment with other subcellular organelles as a broad band, indicated by the distribution of various acid hydrolases, which exhibit subtle heterogeneity among these small lysosomes. The distribution of renin containing granules indicates that in size they represent a distinct subpopulation of small lysosomes. Further fractionation of small lysosomes by equilibrium banding separates two distinct populations at densities 1.20 (small light) and 1.235 g/ml (small dense). Comparison of lysosomal populations fractionated in these studies with the distribution of lysosomal acid hydrolases along the different segments of the nephron suggests that large and small dense lysosomes probably originate from the proximal tubule while the small light lysosomes may contain lysosomes from the distal tubule. Very small, lysosome-like organelles subfractionated from the 'microsomes' may constitute a mixture of small light lysosomes, lysosomal fragments and endocytic vesicles from a variety of cell types. Time course studies with 3H labelled Cd-thionein, following intravenous administration, suggests that uptake in the kidney cortex is very rapid and that catabolism takes place in two distinct phases: rapid breakdown starting in the endosome compartment and slower breakdown in lysosomes. From the association of labelled lysozyme (125I) and Cd-thionein (109Cd) it appears that all the different lysosomal populations identified are at some stage involved with uptake and catabolism of these two proteins.


Evaluation of the efficacy and safety of TAS0313 in adults with recurrent glioblastoma.
TAS0313 is a multi-epitope long peptide vaccine targeting several cancer-associated antigens highly expressed in multiple cancer types, including glioblastoma (GBM). This cohort of a Phase 2 part evaluated the efficacy and safety of TAS0313 in patients with GBM. TAS0313 (27 mg) was administered subcutaneously on Days 1, 8 and 15 of Cycles 1 and 2, and Day 1 of subsequent cycles in 21-day cycles. The primary endpoint was the objective response rate (ORR). The secondary endpoints were the disease control rate, progression-free survival (PFS) and 6- and 12-month progression-free survival rates (PFR) and safety. Immunological response was assessed as an exploratory endpoint. The best overall response was partial response in 1 patient, and the ORR (95% CI) was 11.1% (0.3-48.2%) in the per-protocol set (n = 9). A further 3 patients achieved stable disease, for a disease control rate (95% CI) of 44.4% (13.7-78.8%). Median (95% CI) PFS was 1.7 (1.3-NE) months and 6- and 12-month PFRs (95% CI) were 22.2% (3.4-51.3%) each. Common (≥ 20% incidence) treatment-related adverse events (AEs) were injection site reactions (n = 8, 80.0%), followed by pyrexia (n = 7, 70.0%), and malaise, injection site erythema and injection site pruritus (n = 2, 20.0% each). There were no grade 4 or 5 treatment-related AEs. No deaths occurred during the study. In some patients, TAS0313 treatment was confirmed to increase cytotoxic T lymphocyte and immunoglobulin G levels compared with baseline. TAS0313, a multi-epitope long peptide vaccine, demonstrated promising efficacy and acceptable safety in patients with recurrent GBM. JapicCTI-183824 (Date of registration: Jan 11, 2018).


Longitudinal study of cerebral blood flow SPECT in Parkinson's disease with dementia, and dementia with Lewy bodies.
People with Parkinson's disease (PD) have an increased risk of developing dementia (PDD), which often has clinical features similar to dementia with Lewy bodies (DLB). Whilst perfusion studies have shown parieto-occipital hypoperfusion in DLB and PDD relative to controls, there have not been any longitudinal studies of perfusion changes in PDD and DLB. In this study, we measured brain perfusion using Tc99m HMPAO SPECT over one year in 17 PDD, 18 DLB and 34 healthy subjects. We used SPM99 to compare perfusion changes in the two dementia groups against the control group. We did not see any reductions in perfusion in either of the dementia groups. However, in the DLB, but not PDD group, there was a significant increase in putamen perfusion relative to controls over the year. In both DLB and PDD groups, there was a correlation between striatal perfusion increase over the year, and worsening of parkinsonism. Perfusion changes were not secondary to changes in antiparkinsonian medication. The increase in striatal perfusion may be a compensatory change related to decreasing striatal dopaminergic input from the substantia nigra in PDD and DLB, consistent with the increased predominance of rigidity over tremor symptoms in these groups compared with non-demented PD.


Complications of arteriovenous fistula for hemodialysis: an 8-year study.
To assess the frequency and characteristics of complications of arteriovenous fistula (AVF) and their effect on fistula outcome. We retrospectively reviewed 628 AVFs constructed from November 2002 to October 2010 to record the complications and their management options. The association between age, sex, comorbidities (HIV, hypertension, and diabetes), fistula type, and complications was sought. Most patients were males (73.7%). The mean age was 45.3 years. Comorbidities seen included diabetes mellitus (22.12%), hypertension (83.12%), and HIV infection (9.87%). AVFs constructed were mainly radiocephalic (68%) and brachiocephalic (24.9%). The median follow-up period was 275 days. The cumulative patency rate was 76% and 51% at 1 year and 2 years, respectively. Altogether, 211 complications occurred in 16% of the AVFs. Among them, 36.96% were severe, 25.11% moderate, and 43.91% minor. With respect to the time of occurrence, 63.98% were late complications, 12.79% immediate, and 23.22% early. Aneurysms, failure to mature, and thrombosis were the most frequent complications occurring in 26.54%, 14.69%, and 12.79% of cases, respectively. The management options for the complications included the creation of a new access in 36.96%, a temporary catheter before a new AVF in 10.52%, and nonoperative management in 43.12%. We found no adverse effect of comorbid factors such as diabetes mellitus (χ(2) = 3.58, P > 0.05) or HIV-positive status (χ(2) = 0.64, P > 0.05) on the complication rate. This study shows an overall frequency of complications of 16%. These results show the potential for low complication rate of AVF in selected population.


Substituted hippurates and hippurate analogs as substrates and inhibitors of peptidylglycine alpha-hydroxylating monooxygenase (PHM).
Peptidyl alpha-hydroxylating monooxygenase (PHM) functions in vivo towards the biosynthesis of alpha-amidated peptide hormones in mammals and insects. PHM is a potential target for the development of inhibitors as drugs for the treatment of human disease and as insecticides for the management of insect pests. We show here that relatively simple ground state analogs of the PHM substrate hippuric acid (C(6)H(5)-CO-NH-CH(2)-COOH) inhibit the enzyme with K(i) values as low as 0.5microM. Substitution of sulfur atom(s) into the hippuric acid analog increases the affinity of PHM for the inhibitor. Replacement of the acetylglycine moiety, -CO-NH-CH(2)-COOH with an S-(thioacetyl)thioglycolic acid moiety, -CS-S-CH(2)-COOH, yields compounds with the highest PHM affinity. Both S-(2-phenylthioacetyl)thioglycolate and S-(4-ethylthiobenzoyl)thioglycolic acid inhibit the proliferation of cultured human prostate cancer cells at concentrations >100-fold excess of their respective K(i) values. Comparison of K(i) values between mammalian PHM and insect PHM shows differences in potency suggesting that a PHM-based insecticide with limited human toxicity can be developed.


Notes on testing non-inferiority under the partial verification design with a confirmatory procedure limited to screen positives.
When a new test with fewer invasions or less expenses to administer than the traditional test is developed, we may be interested in testing whether the former is non-inferior to the latter with respect to test accuracy. We define non-inferiority via both the odds ratio (OR) of correctly identifying a case and the OR of correctly identifying a non-case between two tests under comparison. We focus our discussion on testing the non-inferiority of a new screening test to a traditional screening test when a confirmatory procedure is performed only on patients with screen positives. On the basis of well-established methods for paired-sample data, we derive an asymptotic test procedure and an exact test procedure with respect to the two ORs defined here. Using Monte Carlo simulation, we evaluate the performance of these test procedures in a variety of situations. We note that the test procedures proposed here can also be applicable if we are interested in testing non-inferiority with respect to the ratio of sensitivities and the ratio of specificities. We discuss interval estimation of these ORs and sample size calculation based on the asymptotic test procedure considered here. We use the data taken from a study of the prostate-specific-antigen (PSA) test and the digital rectal examination (DRE) test to illustrate the practical use of these test procedures, interval estimators and sample size calculation formula.


Long-term effects of an Apocynum venetum extract on brain monoamine levels and beta-AR density in rats.
The present study was designed to get further insight into the mode of antidepressant action of an extract prepared of the leaves of Apocynum venetum L. (AV). To evaluate biochemical changes, we used a high-performance liquid chromatography system to examine the effects of short-term (2 weeks) and long-term (8 weeks) administration of imipramine (15 mg/kg po) and an AV-extract (15, 60 and 250 mg/kg) on regional levels of serotonin (5-HT), norepinephrine (NE), dopamine (DA) and their metabolites in the rat hypothalamus, striatum and hippocampus. Pronounced changes in 5-HT, NE and DA levels were detected mainly after 8 weeks of daily imipramine treatment. Similar to imipramine, AV-extract reduced NE and DA concentrations after 8 weeks, whereas it failed to affect 5-HT levels. We speculate that the decrease in NE levels after chronic AV treatment might be based partly on the subsensitivity of presynaptic alpha(2)-receptors. In addition to the determination of central monoamine concentrations, quantitative radioligand receptor-binding studies were used to examine the effects of long-term administration of imipramine and AV-extract on beta-adrenergic binding in rat frontal cortex. [125I]CYP binding to beta-adrenergic receptors was found to be decreased after 8 weeks treatment with imipramine, whereas AV-extract had no effect on beta-receptor binding.


CCL5 mRNA is a marker for early fibrosis in chronic hepatitis C and is regulated by interferon-α therapy and toll-like receptor 3 signalling.
Mechanisms causing liver fibrosis during chronic hepatitis C virus infection (cHCV) are not sufficiently understood. This study was aimed to identify biomarkers for early fibrosis (EF) and to investigate their potential role in cHCV-related fibrogenesis. To this end, peripheral whole blood (PB) samples from 36 patients with cHCV recruited from two independent cohorts were subjected to microarray analysis 12 h before initiation of peginterferon-alpha (Peg-IFN-α) and ribavirin therapy. Liver biopsies were evaluated using the Batts-Ludwig staging (BL-S) classification system for fibrosis. We showed that gene expression profiles (N = 8) distinguished between EF (BL-S: 0,1) and late fibrosis (LF; BL-S: 2,3,4) with 88.9% accuracy. Fibrosis-related functional annotations for chemokine-'C-C-motif'' ligand 5 (CCL5) provided foundation for focused investigation, and qRT-PCR confirmed that CCL5 mRNA levels (PB) reliably discriminate EF from LF (accuracy: 86.7%). Positive correlations (P < 0.05) with CCL5 mRNA levels and EF discovered gene expression profiles (PB) reflecting stable expression of IFN-α receptor 1, negative regulation of the MyD88-dependent toll-like receptor (TLR) pathway and decreased expression of TLR3 in vivo. Remarkably, Peg-IFN-α suppressed CCL5 mRNA levels (PB) in EF in vivo. These findings along with results from parallel in vitro investigation into the effect of IFN-α or poly I:C (TLR3-agonist) on CCL5 gene expression in hepatic stellate cells (HSC) attest to the multi-site involvement of these pathways in regulating fibrogenesis. In conclusion, we identified novel, reliable biomarkers for EF and exposed functional properties of the molecular network regulating CCL5 biosynthesis in peripheral or hepatic cell types with key roles in cHCV-related liver and/or immune pathogenesis.


Cross-cultural differences in meter perception.
We examined the influence of incidental exposure to varied metrical patterns from different musical cultures on the perception of complex metrical structures from an unfamiliar musical culture. Adults who were familiar with Western music only (i.e., simple meters) and those who also had limited familiarity with non-Western music were tested on their perception of metrical organization in unfamiliar (Turkish) music with simple and complex meters. Adults who were familiar with Western music detected meter-violating changes in Turkish music with simple meter but not in Turkish music with complex meter. Adults with some exposure to non-Western music that was unmetered or metrically complex detected meter-violating changes in Turkish music with both simple and complex meters, but they performed better on patterns with a simple meter. The implication is that familiarity with varied metrical structures, including those with a non-isochronous tactus, enhances sensitivity to the metrical organization of unfamiliar music.


Clonogenicity of normal and malignant hematopoietic progenitor cells after exposure to synthetic alkyl-lymphospholipids.
Alkyl-lysophospholipids (ALP) are synthetic analogues of natural lysophosphatidylcholine and represent a new class of anti-tumor agents. They are cytotoxic in vitro with a high selectivity for neoplastic cells which, in contrast to normal cells, lack an alkyl-cleavage enzyme to degrade the adsorbed ALP molecules. As ALP accumulates, it interferes with normal membrane phospholipid turnover and eventually causes disruption of membrane integrity. To evaluate the potential value of ALP in eliminating leukemic cells from remission marrows prior to autologous transplantation, we tested the effect of various ALPs on the clongenicity of normal human marrow cells and on promyelocytic leukemia HL-60. A remarkable difference in the dose response to ALP of normal marrow cells an HL-60 was observed. After an incubation period of 24 h, the same inhibition of clonogenicity in HL-60 occurred at ALP concentrations 4 times lower than in normal marrow cells. Reducing the exposure time to 6 h enhanced the selectivity further: whereas HL-60 colonies were nearly completely inhibited at 16 micrograms ALP/ml, more than 50% of normal CFU-c and BFU-E were recovered after incubation with 48 micrograms/ml. No further increase in selectivity was achieved by changing the incubation temperature. Both thioether- and alkyl-analogues were active and no difference was observed between methoxy- and acylamino-substituted ALPs. We conclude that this selective cytotoxicity makes ALP compounds worth further study as purging agents in autologous bone marrow transplantation programs.


Lifetime ovulatory years and ovarian cancer gene expression profiles.
Greater ovulatory years is associated with increased ovarian cancer risk. Although ovulation leads to an acute pro-inflammatory local environment, how long-term exposure to ovulation impacts ovarian carcinogenesis is not fully understood. Thus, we examined the association between gene expression profiles of ovarian tumors and lifetime ovulatory years to enhance understanding of associated biological pathways. RNA sequencing data was generated on 234 invasive ovarian cancer tumors that were high-grade serous, poorly differentiated, or high-grade endometrioid from the Nurses' Health Study (NHS), NHSII, and the New England Case Control Study. We used linear regression to identify differentially expressed genes by estimated ovulatory years, adjusted for birth decade and cohort, overall and stratified by menopausal status at diagnosis. We used false discovery rates (FDR) to account for multiple testing. Gene set enrichment analysis (GSEA) with Cancer Hallmarks, KEGG, and Reactome databases was used to identify biological pathways associated with ovulatory years. No individual genes were significantly differentially expressed by ovulatory years (FDR > 0.19). However, GSEA identified several pathways that were significantly associated with ovulatory years, including downregulation of pathways related to inflammation and proliferation (FDR < 1.0 × 10-5). Greater ovulatory years were more strongly associated with downregulation of genes related to proliferation (e.g., E2F targets, FDR = 1.53 × 10-24; G2M checkpoints, FDR = 3.50 × 10-22) among premenopausal versus postmenopausal women at diagnosis. The association of greater ovulatory years with downregulation of genes involved in inflammatory response such as interferon gamma response pathways (FDR = 7.81 × 10-17) was stronger in postmenopausal women. Our results provide novel insight into the biological pathways that link ovulatory years to ovarian carcinogenesis, which may lead to development of targeted prevention strategies for ovarian cancer.


Intestinal and multivisceral retransplantation results: literature review.
Intestinal/multivisceral transplantation (IT/MVT) is the gold standard treatment for patients with intestinal failure and complications related to total parenteral nutrition, gastrointestinal inoperable indolent tumors, or diffuse portal trombosis. Currently, the reported 1-year patient survival rate is around 80%, similar to other solid organ abdominal transplantations. Unfortunately, the patient survival decreases after the first year with the 5-year rate not close to 70% yet. Acute cellular rejection is the main cause of graft loss. Its early diagnosis may make it possible to improve survival of retransplantations. To analyze the reported results published in the last 5 years by leading transplant centers to evaluate IT/MVT retransplantation results. We performed a literature review using PubMed focusing on multivisceral and intestinal retransplantation in articles published between 2006 and 2012. In relation to the first transplantation, we analyzed demographics, imunosuppression, rejection, infection as well as graft and patient survival rates. Two centers reported results on intestinal and multivisceral retransplantations. Mazariegos et al reported their experience with 15 intestinal retransplantations in 14 pediatric recipients. Four patients died from posttransplant lymphoperliferative disease, severe acute cellular rejection, fungal sepsis, or bleeding from a pseudoaneurysm at a mean time of 5.7 months post-transplantation. Total parenteral nutrition was weaned at a median time of 32 days. Abu-Elmaged et al reported 47 cases with a 5-year survival of 47% for all retransplant modalities. Retransplantation with liver-contained visceral allograft achieved a 5-year survival rate of 61% compared with 16% for liver-free visceral grafts. Despite those huge improvements, some transplanted patients develop severe acute cellular rejection, culminating in graft loss and retransplantation. Repots on multivisceral and intestinal retransplantation outcomes suggest that it is a viable procedure with appropriate patient survival after primary graft loss.


Role of the liver in regulation of body cysteine and taurine levels: a brief review.
The first-pass metabolism of dietary sulfur amino acids by the liver and the robust upregulation of hepatic cysteine dioxygenase activity in response to an increase in dietary protein or sulfur amino acid level gives the liver a primary role in the removal of excess cysteine and in the synthesis of taurine. Hepatic taurine synthesis is largely restricted by the low availability of cysteinesulfinate as substrate for cysteinesulfinate decarboxylase, and taurine production is increased when cysteinesulfinate increases in response to an increase in the hepatic cysteine concentration and the associated increase in cysteine dioxygenase activity. The upregulation of cysteine dioxygenase in the presence of cysteine is a consequence of diminished ubiquitination of cysteine dioxygenase and a slower rate of degradation by the 26S proteasome.


Production of ascorbic acid, total protein, callus and root in vitro of non-heading Chinese cabbage by tissue culture.
The objective of the present work was the selection of cultivar, suitable medium and explant type for callus, root production, ascorbic acid, total ascorbic acid, dehydroascorbic and total protein of non-heading Chinese cabbage in two cultivars 'Caixin' and 'Suzhouqing'. We compared 10 types of MS media supplemented with 0.0, 1.0, 2.0 and 3.0 mg/l TDZ; 0.0, 0.25, 0.50 and 1.0 mg/l NAA and 0.0, 5.0, 7.5 and 9.0 mg/l AgNO3 and 5 kinds of explants as embryo, leaf, root, cotyledon and hypocotyl. Maximum frequency of callus fresh weight was recorded with hypocotyl explant, which were cultured on MS + 2.0 mg/l TDZ + 1.0 mg/l NAA + 9.0 mg/l AgNO3 in 'Suzhouqing', optimum callus dry weight was obtained on the same media. The highest result for root fresh and dry weight recorded with 'Caixin' with MS + 3.0 mg/l TDZ + 1.0 mg/l NAA + 9.0 mg/l AgNO3 when we used embryo as explant. The highest ascorbic acid content was found with callus cultured on MS + 1.0 mg/l TDZ + 0.25 mg/l NAA + 5.0 mg/l AgNO3, when used leaf explant in 'Caixin' or root in 'Suzhouqing', and there were no significant difference between them. While the highest value of total AsA content was registered with callus cultured on MS + 2.0 mg/l TDZ + 0.25 mg/l NAA + 5.0 mg/l AgNO3 extracted from cotyledon in 'Caixin'. The highest content of DHA was registered with MS + 2.0 mg/l TDZ + 0.25 mg/l NAA + 5.0 mg/l AgNO3 with cotyledon in 'Caixin'. Also, in 'Caixin' MS + 3.0 mg/l TDZ + 0.25 mg/l NAA + 5.0 mg/l AgNO3 recorded the highest value of total protein content with embryo explant.


PD-L1 and PD-L2 immune checkpoint protein induction by type III interferon in non-small cell lung cancer cells.
Despite the clinical success of PD-1/PD-1-ligand immunotherapy in non-small cell lung cancer (NSCLC), the appearance of primary and acquired therapy resistance is a major challenge reflecting that the mechanisms regulating the expression of the PD-1-ligands PD-L1 and PD-L2 are not fully explored. Type I and II interferons (IFNs) induce PD-L1 and PD-L2 expression. Here, we examined if PD-L1 and PD-L2 expression also can be induced by type III IFN, IFN-λ, which is peculiarly important for airway epithelial surfaces. In silico mRNA expression analysis of PD-L1 (CD274), PD-L2 (PDCD1LG2), and IFN- λ signaling signature genes in NSCLC tumors and cell lines was performed using RNA sequencing expression data from TCGA, OncoSG, and DepMap portals. IFN-λ-mediated induction of PD-L1 and PD-L2 expression in NSCLC cell lines was examined by real-time quantitative polymerase chain reaction and flow cytometry. IFNL genes encoding IFN- λ variants are expressed in the majority of NSCLC tumors and cell lines along with the IFNLR1 and IL10R2 genes encoding the IFN-λ receptor subunits. The expression of PD-L1 and PD-L2 mRNA is higher in NSCLC tumors with IFNL mRNA expression compared to tumors without IFNL expression. In the NSCLC cell line HCC827, stimulation with IFN-λ induced both an increase in PD-L1 and PD-L2 mRNA expression and cell surface abundance of the corresponding proteins. In the NSCLC cell line A427, displaying a low basal expression of PD-L1 and PD-L2 mRNA and corresponding proteins, stimulation with IFN-λ resulted in an induction of the former. The type III IFN, IFN- λ, is capable of inducing PD-L1 and PD-L2 expression, at least in some NSCLC cells, and this regulation will need acknowledgment in the development of new diagnostic procedures, such as gene expression signature profiles, to improve PD-1/PD-1-ligand immunotherapy in NSCLC.


Evaluation of the antiwear-ability/scratch-resistance efficacy of makeup products by in vitro test method application.
The objective of this study is to propose a method for assessing the antiwear-ability (AW) or surface scratch-resistance (SR) efficacy of makeup products through in vitro experiments. The method primarily involves measuring the change in weight as a means of evaluating the overall effectiveness. AW/SR effects are evaluated by applying a fixed amount of makeup product on artificial fake skin and comparing the weight difference after simulated friction/scratch. The in vitro results indicate that this method is easy to operate and yields repeatable data. It consistently reflects differences between samples when compared to clinical studies. This method effectively compares the AW/SR effects of makeup products and demonstrates utility in evaluating product efficacy and difference. It holds great scientific and practical value.


Oxidized low-density lipoprotein (LDL) enhances thromboxane A(2) synthesis by platelets, but lysolecithin as a product of LDL oxidation has an inhibitory effect.
Oxidation of low-density lipoprotein (LDL) by copper sulfate led to a significant increase in lysophosphatidylcholine (lyso PC) at the expense of phosphatidylcholine. Incubation of different concentrations of oxidized LDL (oxLDL) (32-650 microg protein/ml) with platelets for 1 h at 37 degrees C increased lyso PC content. The increase was dependent on oxLDL concentration. Incubation of platelets with various concentrations of lyso PC in solution for 5 or 15 min showed that lyso PC percentage was increased in the platelet membrane and the increase was dose dependent. Platelets incubated with various concentrations of lyso PC (2-100 microM) for 5 or 15 min and then triggered with thrombin also showed a significant decrease of thromboxane A(2) (TXA(2)) release as lyso PC concentration reached 10 microM or 6 microM, respectively. The decrease of TXA(2) release was more significant as lyso PC concentration was increased. The present study showed that this inhibition of TXA(2) release by lyso PC was due to 1) inhibition of phospholipase A(2) and the decrease of free arachidonic acid liberation from platelet phospholipid and 2) inhibition of cyclooxygenase. These inhibitory effects of lyso PC were discussed in relation to its effect on membrane fluidity. Lyso PC at concentrations of 30, 50, and 100 microM caused a sudden drop in TXA(2) release and a sudden increase of lactic dehydrogenase loss from the platelets due to their lysis and inhibition of cyclooxygenase enzyme. The present study shows that oxLDL contains high levels of lyso PC that are transferable to the platelets and can weaken their responsiveness to thrombin and decrease TXA(2) release. In our previous study, we found that oxLDL also contained high levels of oxysterols and thiobarbituric acid reactive substances (TBARS), which enhanced platelet reactivity to thrombin and increased TXA(2) release. We conclude that the net effect of oxLDL on platelets will depend on its degree of oxidation and the ratio between oxysterols plus TBARS/lyso PC. Variations in this ratio may explain some of the contradictions cited in the literature concerning the effect of oxLDL on platelet activation.


The potential of the endolysin Lysdb from Lactobacillus delbrueckii phage for combating Staphylococcus aureus during cheese manufacture from raw milk.
Phage endolysins have received increased attention in recent times as potential antibacterial agents and the biopreservatives in food production processes. Staphylococcus aureus is one of the most common pathogens in bacterial food poisoning outbreaks. In this study, the endolysin Lysdb, one of the two-component cell lysis cassette of Lactobacillus delbrueckii phage phiLdb, was shown to possess a muramidase domain and catalytic sites with homology to Chalaropsis-type lysozymes. Peptidoglycan hydrolytic bond specificity determination revealed that Lysdb was able to cleave the 6-O-acetylated peptidoglycans present in the cell walls of S. aureus. Turbidity reduction assays demonstrated that Lysdb could effectively lyse the S. aureus live cells under acidic and mesothermal conditions. To further evaluate the ability of Lysdb as a potential antibacterial agent against S. aureus in cheese manufacture, Lactobacillus casei BL23 was engineered to constitutively deliver active Lysdb to challenge S. aureus in lab-scale cheese making from raw milk. Compared with the raw milk, the viable counts of S. aureus were reduced by 10(5)-fold in the cheese inoculated with the engineered L. casei strain during the fermentation process, and the pathogenic bacterial numbers remained at a low level (10(4) CFU/g) after 6 weeks of ripening at 10 °C. Taken together, all results indicated that the Lysdb has the function as an effective tool for combating S. aureus during cheese manufacture from raw milk.


Prevalence of mild behavioural impairment domains: a meta-analysis.
Mild behavioural impairment (MBI) is a neurobehavioural syndrome characterised by later life emergence of persistent neuropsychiatric symptoms. Our previous meta-analysis showed that MBI is prevalent among cognitively normal (CN), subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) subjects. This study is to calculate the pooled prevalence of MBI domains among CN, SCI, and MCI subjects. A search of relevant literature published between 1 January 2003 and 6 August 2021 was conducted. Meta-analysis using a random effects model and meta-regression was performed. Ten studies conducted among 12 067 subjects (9758 CN, 1057 SCI and 1252 MCI) with retrievable MBI domains data underwent meta-analysis, revealing pooled prevalence of affective dysregulation (AFD), impulse dyscontrol (IDS), decreased motivation (DMT), social inappropriateness (SIP) and abnormal perception/thought (APT) of 32.84% (95% CI 24.44-42.5%), 26.67% (95% CI 18.24-37.23%), 12.58% (95% CI 6.93-21.75%), 6.05% (95% CI 3.44-10.42%), and 2.81% (95% CI 1.67-4.69%) respectively. AFD and APT domains demonstrated ordinal increase in pooled prevalence from CN, SCI and MCI subgroups, but meta-regression demonstrated no significant difference in MBI domains prevalence among cognitive subgroups (in contrast to the significant increase in MBI prevalence from CN to SCI to MCI). The pooled prevalence of AFD and IDS are greater than that of DMT, SIP and APT among all cognitive subgroups. Several variables were found to explain the high heterogeneity. AFD and IDS are the two most prevalent MBI domains and remain the same with cognitive deterioration. This finding is potentially relevant to clinical practice.


Surgical lessons learned from the treatment of atrial fibrillation.
In 1987, the MAZE procedure was introduced into clinical practice by Dr. James Cox. Prior procedures included AV node ablation and other procedures that had major limitations. The clinical success of the MAZE procedure was over 90% in most series. Adoptability was limited by its technical complexity. With the introduction of a variety of energy sources to replace the "cut and sew" lines of ablation without sacrificing clinical success, the procedure has been widely adopted in conjunction with other cardiac operations ("concomitant" Maze procedures). Surgical techniques for "stand alone" procedures continue to evolve as the technology to perform the procedure less invasively is developed.


Epidemiologic and phenomenological aspects of post-traumatic stress disorder: DSM-III-R diagnosis and diagnostic criteria not validated.
The aim of this cohort study was: (i) to validate the diagnostic criteria for post-traumatic stress disorder (PTSD) of the DSM-III-R; and (ii) to examine the incidence rate of PTSD in a study population exposed to two different traumatic events, i.e. a fire in a hotel ball-room and a multiple collision car-crash on a Belgian highway. One hundred and eighty-five victims (130 fire and 55 car accident victims) were assessed between 7 and 9 months after the traumatic event using the Composite International Diagnostic Interview (CIDI), PTSD Module, a fully structured diagnostic interview for the assessment of PTSD according to DSM-III-R criteria. Twenty-three percent of the study population met DSM-III-R criteria for PTSD. By means of unsupervised and supervised multivariate statistical analyses we were unable to validate the three-factorial structure, i.e. criteria B, C and D, of the DSM-III-R PTSD diagnosis. The latter relies heavily on the C diagnostic criteria, which appear to be too restrictive. Women were more likely to develop symptoms of reexperience (B) and arousal (D) than men. There was a significantly higher incidence of criteria B, C and D, but not of PTSD, in fire than in car-accident victims. Between 42 and 57% of the victims developed the first PTSD symptoms on the day of the trauma; within the next week these incidence rates increased to 77.1, 57.8 and 73.5% for criteria B, C and D, respectively. In conclusion, this study was unable to demonstrate the validity of the diagnostic criteria for PTSD according to DSM-III-R. The present cohort study has defined a number of factors that may predict new occurrences of PTSD symptoms after a traumatic event, i.e. gender, type of trauma and time delay between the trauma and the assessment of the diagnostic criteria.


Immune hallmarks of rheumatoid arthritis management: A brief review.
The purpose of this review was to examine current evidence on immunomodulation mediated by conventional drugs and the use of novel biological agents for the treatment of rheumatoid arthritis (RA). Currently, treatment is focused on maximizing quality of life through sustained clinical remission and/or attenuating disease activity. To do so, disease-modifying antirheumatic drugs, especially methotrexate, are used alone or in combination with other drugs, including leflunomide, biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs). The most recent strategies modulate the immune response of the individual RA patient using tsDMARDs such as JAK inhibitors and bDMARDs such as ig-CTLA-4, anti- IL6R, anti-TNF-α and anti-CD20. To better understand current immunopharmacological interventions, we also looked at documented mechanisms of RA-mediated immunomodulation, highlighting perspectives potentially boosting RA treatment.


[Iron infusion - step by step].
In many general medical practices, iron infusions are still regarded as the treatment of choice for iron deficiency. However, they are only very rarely indicated and are often prescribed without a medical basis. This article shows the correct procedure for intravenous iron administration if it is really indicated.


Guideline concordance of treatment for depressive disorders in Canada.
Depression is one of the most prevalent mental health problems worldwide with considerable social and economic burdens. While practice guidelines exist, their adherence is inconsistent in clinical practice. To provide up-to-date national estimates of the adequacy of treatment received by Canadians having suffered a major depressive disorder (MDD) and examine factors associated with this adequacy. To evaluate the impact of different definitions of guideline-concordant treatment on the results. Data were drawn from the Canadian Community Health Survey, cycle 1.2: Mental Health and Well-Being (CCHS 1.2), a nationally representative survey conducted in 2002 and targetting persons aged 15 years or older living in private dwellings. In order to calculate the prevalence of treatment adequacy, we used a sample of 1,563 individuals meeting the criteria for MDD in the 12 months preceding the survey. A subset of 831 subjects who reported having used health services for mental health purposes at least once during that time served to identify the factors associated with treatment adequacy. Four definitions of minimally adequate treatment were considered and covariates were selected according to a well-known behavioral model. The analyses consisted of prevalence estimates and logistic regression models. Among selected subjects, 55% received guideline-concordant treatment according to the Canadian guidelines. Inadequacy was more prevalent in rural settings, for less complex cases, and in the general medical sector. Depending on the definition, prevalence of guideline-concordant treatment ranged between 48 and 71%, and factors associated with guideline-concordant treatment were mainly need factors and sector of care. A large proportion of people with a depressive disorder do not receive minimally adequate treatment. Improved access to and quality of treatment is required, especially in primary care settings.


Coronary thrombosis: pathogenesis and prevention.
Acute myocardial infarction is most commonly initiated by fissuring of an atheromatous plaque. Through such fissures the blood is exposed to thrombogenic constituents of the intima, causing thrombotic obstruction of the coronary artery. Why plaque fissuring occurs is not known. Our investigation is to establish which types of plaque undergo fissuring by relating their mechanical with their cellular and biochemical properties; and to quantify the distribution of fissures. Results so far indicate that fissures occur predominantly in plaques with lipid pools in one segment of intima, and that the commonest single site of fissuring is that of maximal stress concentration as predicted by computer modelling. The results also suggest that arterial spasm at the immediate site of fissuring is not involved, as more than half the fissures occur at sites where there is no residual medial smooth muscle. Obstructive coronary thrombosis is initiated in most cases by plaque fissure with local haemorrhage which induces intravascular platelet aggregation. Recent observations with novel techniques have provided evidence that platelet aggregation in vivo is initiated by ADP and potentiated by thromboxane A2 and thrombin, with actual contribution of exposed collagen still undetermined. These observations provide an explanation for the limited effectiveness of any simple platelet-inhibiting drug, including Aspirin, by itself whenever arterial, eg. coronary or cerebral thrombosis is initiated by haemorrhages into atheromatous plaques. On the other hand, Aspirin is significantly effective when myocardial infarction follows unstable angina and when strokes follow transient episodes of cerebral ischaemia.(ABSTRACT TRUNCATED AT 250 WORDS)


Correlation of Stiffness of Prostate Cancer Measured by Shear Wave Elastography with Grade Group: A Preliminary Study.
The aim of study was to explore the correlation between shear wave elastography (SWE) and grade group (GG) of prostate cancer (PCa). This retrospective study involved prostate-specific antigen elevated patients with elevated prostate-specific antigen levels who underwent SWE before transrectal ultrasound-guided needle biopsy. A total of 49 PCa lesions were reviewed after radical prostatectomy; 3-7 regions of interest were placed within the cancerous area on axial view compared with the tumor foci outlined on the slides by pathologist. The maximum SWE value was measured, quantitative SWE parameters (Emax, Emean, Emin and standard deviation [SD]) were recorded and correlated with GG and then parameters were compared between indolent (≤2) and aggressive (≥3) GGs. The diagnostic value of each parameter was compared with the receiver operating characteristic curve. Forty-nine PCa foci were divided into two groups on the basis of their GGs. All SWE parameters exhibited a significant linear trend with GG. The area under the receiver operating characteristic curve (AUC) was 0.816 for Emax; with a cutoff point of 84 kPa, sensitivity and specificity were 81.3% and 82.4% to differentiate low and high GGs in PCa. The AUC was 0.776 for Emean; with a cutoff point of 71 kPa, sensitivity and specificity were 78.1% and 76.5%. For Emin, the AUC was 0.739; with a cutoff point of 60 kPa, sensitivity and specificity were 68.8% and 70.6%. For SD, the AUC was 0.681; with a cutoff point of 8.3 kPa, sensitivity and specificity were 46.9% and 94.1%. There were no significant differences between the four SWE parameters (p < 0.05 for all). SWE features were correlated with GGs, and this correlation may have excellent diagnostic performance in predicting high GG in PCa.


In vitro activity of carvacrol in combination with meropenem against carbapenem-resistant Klebsiella pneumoniae.
Carbapenem resistance observed in Klebsiella pneumoniae strains limits treatment options. Therefore, use of antibiotics combined with bioactive compounds may be an important strategy to control K. pneumoniae. The purpose of this study was to evaluate the activity of combination of carvacrol and meropenem on carbapenem-resistant K. pneumoniae (CRKP) strains. The presence of blaOXA-48 carbapenemase in all 25 CRKP strains was identified using the PCR technique. The combination of carvacrol and meropenem was tested for antimicrobial activity on CRKP strains. The minimum inhibitory concentrations of carvacrol and meropenem were detected within a range of 32-128 µg/mL using the broth microdilution method. Synergy between carvacrol and meropenem was observed on 8 of the 25 CRKP strains by checkerboard assay (FICI = 0.5) and confirmed by time-kill assay. According to the live-dead test results, the viability percentage of the cells exposed to synergistic combination was 35.47% at the end of 24 h. The membrane damage caused by the synergistic combination was spectrophotometrically measured (A = 0.21) and further confirmed by SEM analysis. According to the MTT assay, both carvacrol and meropenem did not show any statistically significant cytotoxic effect on Vero cells (p > 0.05). In conclusion, the results suggest that carvacrol and meropenem can act synergistically to inhibit the growth of CRKP.


Lactic acidosis: Clinical implications and management strategies.
In hospitalized patients, elevated serum lactate levels are both a marker of risk and a target of therapy. The authors describe the mechanisms underlying lactate elevations, note the risks associated with lactic acidosis, and outline a strategy for its treatment.


Effects of HMG-CoA reductase inhibitors on skeletal muscles of rabbits.
This study was undertaken to evaluate the potential of HMG-CoA reductase inhibitors, pravastatin sodium (hereafter abbreviated to pravastatin) and simvastatin, for induction of myopathy and influence on the ubiquinone content of skeletal and cardiac muscles and other tissues in the rabbit. Both drugs were administered orally to New Zealand White rabbits (n = 5) at the dose of 50 mg/kg per day for 14 days. Serum cholesterol levels in the pravastatin- and simvastatin-treated groups were reduced significantly by 47% an 58% on day 14 (P < 0.05), respectively, as compared with the control group, but the difference between the two treatment groups was not significant. In animals of the simvastatin-treated group, abnormal elevations of creatine kinase (CK) and lactate dehydrogenase (LDH) levels were observed, in association with severe lesions in skeletal muscles, but not cardiac muscle. The ubiquinone content in skeletal muscle in this treatment group was not affected, even in the muscles that had severe lesions, whereas that in liver and cardiac muscle was significantly reduced compared with the control group. The results suggest that there is no direct correlation between myopathy and the decrease of ubiquinone content in skeletal muscles. In contrast, the animals in the pravastatin-treated group did not show any changes in CK and LDH levels, ubiquinone content in liver and muscles, or in histopathological features of muscle fibers. The difference between the adverse effects seen with the two drugs could be attributed to physicochemical properties: simvastatin permeates the plasma membrane because of its hydrophobic nature, whereas pravastatin does not, because it is hydrophilic.


Evaluation of diphenylamine derivatives in apple peel using gradient reversed-phase liquid chromatography with ultraviolet-visible absorption and atmospheric pressure chemical ionization mass selective detection.
A method was developed for extracting, identifying, and quantifying diphenylamine (DPA) derivatives in the peel of DPA-treated apples using gradient reversed-phase liquid chromatography with ultraviolet-visible absorption and atmospheric pressure chemical ionization detection (LC-UV-vis-APCI-MS). Compounds routinely analyzed using this method included hydroxylated, nitrosated, nitrated, and methoxylated diphenylamine derivatives. Analysis of peel treated with 0-8 g L(-1) DPA showed that peel DPA content was a limiting factor in derivative production and that recovery of most compounds over this range was linear.


[Pylephlebitis related to acute appendicitis. Case and review].
The pilephlebitis is the septic thrombophlebitis of the portal venous system ranging from asymptomatic to severe complications. Diagnosed based on imaging tests, and their treatment is based on antibiotics and anticoagulant therapy. 24 years male, appendectomy 12 days before. Readmission for 3 days with fever, jaundice and choluria; hyperbilirrubinemia. Intravenous contrast CT is performed, showed thrombus in portal, splenic and mesenteric vein system. Diagnosis of pylephlebitis is established, initiating managed with antibiotics and anticoagulant, with favorable clinical outcome. The pylephlebitis has an estimated incidence of 2.7 cases per year, with an unspecified clinical picture ranging from asymptomatic to severe cases with septic shock and hepatic failure. There may be accompanying fever and abdominal pain in more than 80% of the cases and presenting in some cases with leukocytosis and hyperbilirrubinemia. Intravenous contrast CT is the gold standard. The treatment is based on 4 points: Septic focus control, antibiotics, early anticoagulant and resolution of complications. The pylephlebitis should be taken into consideration as a possible secondary complication of intraabdominal infections. A timely diagnosis with a imaging tests and apply treatment reduce their morbidity and mortality.


[Lysosomes-like thrombocyte alpha-granules: the activation and inhibition of the release of the contents in blood coagulation].
The mechanism of the release of alpha-granules constituents of thrombocytes was studied in the course of blood coagulation utilizing the fluorometric technique. The release reaction can be induced by proteolytic enzymes. The process is stimulated by the presence of extracellular Ca2+. This pattern of release reaction belongs to "release II" type. Aminazin can also induced release of alpha-granules constituents. Heparin inhibited release II induced by Ca2+ in citrated plasma, whereas streptase had no effect.


Long-term follow-up in 54 surgically treated patients with gastrointestinal stromal tumours.
Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the alimentary tract. Since these tumours are rather resistant to radiation and conventional chemotherapy, prognosis may be poor. Imatinib, a KIT tyrosine kinase inhibitor, has been shown to have dramatic antitumour effects on GISTs; however, surgical en bloc resection of the tumour with free resection margins remains still the first option for cure. Here, we present a retrospective study with 54 consecutive GIST patients who were treated surgically at our University Hospital between 1993 and 2005 and were followed up at 5 and 10 years. The disease-specific survival rate was 94% at 1 year, 91% at 3 years, 76% at 5 years, and 72% at 10 years. In univariate analysis, tumour size, mitotic rate, morphology, and necrosis predicted survival in patients with negative margins. Age, sex, and symptoms did not influence outcome. GISTs have a high incidence of associated secondary malignancies which may have a significant influence on prognosis and outcome. Patients with R0 resections had a significantly better survival rate of 86% at 5 years and of 81% at 10 years than those with R1 and R2 resections (21% and 0%).


Clinical usefulness of Artronix brain scanner multiplanar coronal and sagittal brain images.
The Artronix 1,100 head scanner is a promising unit which allows reconstitution of the images in coronal and sagittal planes from the axial slice. The clinical usefulness of coronal and sagittal images thus obtained is illustrated and discussed.


Estimation of fetal weight in utero from symphysis-fundal height and abdominal girth measurements.
The ability to estimate fetal weight accurately from symphysis-fundal height (SFH) and abdominal girth (AG) measurements was evaluated. Multivariate regression analysis was performed on measurements made on 208 primigravidas within 48 hours of delivery. A better correlation with birth-weight was obtained with the SFH than with the AG. The equation BW = -1.515 + 0.092 (SFH) + 0.016 (AG) yielded a coefficient of multiple correlation of 0.7259. Using this equation, the mean percentage prediction errors were 5.7% +/- 4.2(SD) in fetuses between 2,500 and 3,500 g (n = 156), 9.4% +/- 5.25(SD) in those larger than 3,500 g (n = 33), and 19.1% +/- 8.2(SD) in those smaller than 2,500 g (n = 19). All the generated equations similarly underestimated the fetal weight in the larger babies and overestimated in the smaller babies. Inclusion of quadratic and logarithmic functions as well as skin-fold thickness measurements into the equations did not decrease the error or alter the distribution of errors. It was concluded that although fetal weight estimation may be reasonably accurate between 2,500 g and 3,500 g, the error is too great for the method to be clinically useful in the smaller and larger babies. Moreover, a theoretical basis for a high sensitivity in the detection of small for dates fetuses from these parameters would be difficult to establish.


Transitions between epithelial and mesenchymal states in development and disease.
The ancestors of modern Metazoa were constructed in large part by the foldings and distortions of two-dimensional sheets of epithelial cells. This changed approximately 600 million years ago with the evolution of mesenchymal cells. These cells arise as the result of epithelial cell delamination through a reprogramming process called an epithelial to mesenchymal transition (EMT) [Shook D, Keller R. Mechanisms, mechanics and function of epithelial-mesenchymal transitions in early development. Mech Dev 2003;120:1351-83; Thiery JP, Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol 2006;7:131-42]. Because mesenchymal cells are free to migrate through the body cavity, the evolution of the mesenchyme opened up new avenues for morphological plasticity, as cells evolved the ability to take up new positions within the embryo and to participate in novel cell-cell interactions; forming new types of internal tissues and organs such as muscle and bone [Thiery JP, Sleeman, JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol 2006;7:131-42; Hay ED, Zuk A. Transformations between epithelium and mesenchyme: normal, pathological, and experimentally induced. Am J Kidney Dis 1995;26:678-90]. After migrating to a suitable site, mesenchymal cells coalesce and re-polarize to form secondary epithelia, in a so-called mesenchymal-epithelial transition (MET). Such switches between mesenchymal and epithelial states are a frequent feature of Metazoan gastrulation [Hay ED, Zuk A. Transformations between epithelium and mesenchyme: normal, pathological, and experimentally induced. Am J Kidney Dis 1995;26:678-90] and the neural crest lineage [Duband JL, Monier F, Delannet M, Newgreen D. Epitheliu-mmesenchyme transition during neural crest development. Acta Anat 1995;154:63-78]. Significantly, however, when hijacked during the development of cancer, the ability of cells to undergo EMT, to leave the primary tumor and to undergo MET at secondary sites can have devastating consequences on the organism, allowing tumor cells derived from epithelia to invade surrounding tissues and spread through the host [Thiery JP, Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol 2006;7:131-42; Hay ED, Zuk A. Transformations between epithelium and mesenchyme: normal, pathological, and experimentally induced. Am J Kidney Dis 1995;26:678-90]. Thus, the molecular and cellular mechanisms underpinning EMT are both an essential feature of Metazoan development and an important area of biomedical research. In this review, we discuss the common molecular and cellular mechanisms involved in EMT in both cases.


A validated reduced-order dynamic model of nitric oxide regulation in coronary arteries.
Nitric Oxide (NO) provides myocardial oxygen demands of the heart during exercise and cardiac pacing and also prevents cardiovascular diseases such as atherosclerosis and platelet adhesion and aggregation. However, the direct in vivo measurement of NO in coronary arteries is still challenging. To address this matter, a mathematical model of dynamic changes of calcium and NO concentration in the coronary artery was developed for the first time. The model is able to simulate the effect of NO release in coronary arteries and its impact on the hemodynamics of the coronary arterial tree and also to investigate the vasodilation effects of arteries during cardiac pacing. For these purposes, flow rate, time-averaged wall shear stress, dilation percent, NO concentration, and Calcium (Ca2+) concentration within coronary arteries were obtained. In addition, the impact of hematocrit on the flow rate of the coronary artery was studied. It was seen that the behavior of flow rate, wall shear stress, and Ca2+ is biphasic, but the behavior of NO concentration and the dilation percent is triphasic. Also, by increasing the Hematocrit, the blood flow reduces slightly. The results were compared with several experimental measurements to validate the model qualitatively and quantitatively. It was observed that the presented model is well capable of predicting the behavior of arteries after releasing NO during cardiac pacing. Such a study would be a valuable tool to understand the mechanisms underlying vessel damage, and thereby to offer insights for the prevention or treatment of cardiovascular diseases.


Enhancement of adenosine production by Bacillus subtilis CGMCC 4484 through metabolic flux analysis and simplified feeding strategies.
The objective of this research was to understand how the initial glucose concentration influences adenosine (AR) production and metabolic flux shift on the cultivation of Bacillus subtilis CGMCC 4484. Experiments confirmed that initial glucose concentration affects cell growth, AR production and metabolites, significantly. The flux distribution at the key nodes of glucose-6-phosphate (G6P), pyruvate (PYR) and acetyl coenzyme-A (AcCoA) could be affected by changing the glucose concentration. Based on kinetic analysis of specific rates, the low-glucose concentration was better for both cell growth and AR production during the first 12 h. However, the high-glucose concentration was more favorable for AR formation after 18 h. Furthermore, different simplified feeding strategies were designed to achieve higher AR accumulation. The final AR concentration of 15.60 g L(-1) was achieved when an optimized constant-feeding strategy was used, which was 21.02 % higher than batch fermentation. This was the first time to investigate the regulation of the glucose metabolism of AR-producing B. subtilis.


Systemic Lupus Erythematosus Risk: The Role of Environmental Factors.
Systemic lupus erythematosus (SLE) is a complex, chronic autoimmune disease. The etiology of SLE is multifactorial and includes potential environmental triggers, which may occur sequentially (the "multi-hit" hypothesis). This review focuses on SLE risk potentially associated with environmental factors including infections, the microbiome, diet, respirable exposures (eg, crystalline silica, smoking, air pollution), organic pollutants, heavy metals, and ultraviolet radiation.